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6. Table S1 from Brentuximab Vedotin–Driven Microtubule Disruption Results in Endoplasmic Reticulum Stress Leading to Immunogenic Cell Death and Antitumor Immunity

Author

Heiser, Ryan A., primary, Cao, Anthony T., primary, Zeng, Weiping, primary, Ulrich, Michelle, primary, Younan, Patrick, primary, Anderson, Martha E., primary, Trueblood, Esther S., primary, Jonas, Mechthild, primary, Thurman, Robert, primary, Law, Che-Leung, primary, and Gardai, Shyra J., primary

Published
2024
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7. Figure S2 from Brentuximab Vedotin–Driven Microtubule Disruption Results in Endoplasmic Reticulum Stress Leading to Immunogenic Cell Death and Antitumor Immunity

Author

Heiser, Ryan A., primary, Cao, Anthony T., primary, Zeng, Weiping, primary, Ulrich, Michelle, primary, Younan, Patrick, primary, Anderson, Martha E., primary, Trueblood, Esther S., primary, Jonas, Mechthild, primary, Thurman, Robert, primary, Law, Che-Leung, primary, and Gardai, Shyra J., primary

Published
2024
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8. Data from Brentuximab Vedotin–Driven Microtubule Disruption Results in Endoplasmic Reticulum Stress Leading to Immunogenic Cell Death and Antitumor Immunity

Author

Heiser, Ryan A., primary, Cao, Anthony T., primary, Zeng, Weiping, primary, Ulrich, Michelle, primary, Younan, Patrick, primary, Anderson, Martha E., primary, Trueblood, Esther S., primary, Jonas, Mechthild, primary, Thurman, Robert, primary, Law, Che-Leung, primary, and Gardai, Shyra J., primary

Published
2024
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9. Supplementary Data from Brentuximab Vedotin–Driven Microtubule Disruption Results in Endoplasmic Reticulum Stress Leading to Immunogenic Cell Death and Antitumor Immunity

Author

Heiser, Ryan A., primary, Cao, Anthony T., primary, Zeng, Weiping, primary, Ulrich, Michelle, primary, Younan, Patrick, primary, Anderson, Martha E., primary, Trueblood, Esther S., primary, Jonas, Mechthild, primary, Thurman, Robert, primary, Law, Che-Leung, primary, and Gardai, Shyra J., primary

Published
2024
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10. Mouse regulatory DNA landscapes reveal global principles of cis-regulatory evolution

Author

Vierstra, Jeff, Rynes, Eric, Sandstrom, Richard, Zhang, Miaohua, Canfield, Theresa, Hansen, R Scott, Stehling-Sun, Sandra, Sabo, Peter J, Byron, Rachel, Humbert, Richard, Thurman, Robert E, Johnson, Audra K, Vong, Shinny, Lee, Kristen, Bates, Daniel, Neri, Fidencio, Diegel, Morgan, Giste, Erika, Haugen, Eric, Dunn, Douglas, Wilken, Matthew S, Josefowicz, Steven, Samstein, Robert, Chang, Kai-Hsin, Eichler, Evan E, De Bruijn, Marella, Reh, Thomas A, Skoultchi, Arthur, Rudensky, Alexander, Orkin, Stuart H, Papayannopoulou, Thalia, Treuting, Piper M, Selleri, Licia, Kaul, Rajinder, Groudine, Mark, Bender, MA, and Stamatoyannopoulos, John A

Subjects
Biochemistry and Cell Biology, Bioinformatics and Computational Biology, Biological Sciences, Biotechnology, Human Genome, Genetics, Generic health relevance, Animals, Base Sequence, Conserved Sequence, DNA, Deoxyribonuclease I, Evolution, Molecular, Genome, Human, Humans, Mice, Regulatory Sequences, Nucleic Acid, Restriction Mapping, Transcription Factors, General Science & Technology
Abstract

To study the evolutionary dynamics of regulatory DNA, we mapped >1.3 million deoxyribonuclease I-hypersensitive sites (DHSs) in 45 mouse cell and tissue types, and systematically compared these with human DHS maps from orthologous compartments. We found that the mouse and human genomes have undergone extensive cis-regulatory rewiring that combines branch-specific evolutionary innovation and loss with widespread repurposing of conserved DHSs to alternative cell fates, and that this process is mediated by turnover of transcription factor (TF) recognition elements. Despite pervasive evolutionary remodeling of the location and content of individual cis-regulatory regions, within orthologous mouse and human cell types the global fraction of regulatory DNA bases encoding recognition sites for each TF has been strictly conserved. Our findings provide new insights into the evolutionary forces shaping mammalian regulatory DNA landscapes.

Published
2014

11. Nonfucosylation of an anti-TIGIT antibody enhances FcγR engagement, driving innate immune activation and antitumor activity

Author

Smith, Alyson J., primary, Thurman, Robert E., additional, Zeng, Weiping, additional, Grogan, Bryan, additional, Lucas, Sasha, additional, Gutierrez, Guadalupe, additional, Heiser, Ryan A., additional, Wo, Serena W., additional, Blackmarr, Amber, additional, Peterson, Scott, additional, and Gardai, Shyra J., additional

Published
2023
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12. Comprehensive analysis of the chromatin landscape in Drosophila melanogaster

Author

Kharchenko, Peter V, Alekseyenko, Artyom A, Schwartz, Yuri B, Minoda, Aki, Riddle, Nicole C, Ernst, Jason, Sabo, Peter J, Larschan, Erica, Gorchakov, Andrey A, Gu, Tingting, Linder-Basso, Daniela, Plachetka, Annette, Shanower, Gregory, Tolstorukov, Michael Y, Luquette, Lovelace J, Xi, Ruibin, Jung, Youngsook L, Park, Richard W, Bishop, Eric P, Canfield, Theresa K, Sandstrom, Richard, Thurman, Robert E, MacAlpine, David M, Stamatoyannopoulos, John A, Kellis, Manolis, Elgin, Sarah CR, Kuroda, Mitzi I, Pirrotta, Vincenzo, Karpen, Gary H, and Park, Peter J

Subjects
Biotechnology, Human Genome, Genetics, Prevention, Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance, Animals, Cell Line, Chromatin, Chromatin Immunoprecipitation, Chromosomal Proteins, Non-Histone, Deoxyribonuclease I, Drosophila Proteins, Drosophila melanogaster, Exons, Gene Expression Regulation, Genes, Insect, Genome, Insect, Histones, Male, Molecular Sequence Annotation, Oligonucleotide Array Sequence Analysis, Polycomb Repressive Complex 1, RNA, Sequence Analysis, Transcription, Genetic, General Science & Technology
Abstract

Chromatin is composed of DNA and a variety of modified histones and non-histone proteins, which have an impact on cell differentiation, gene regulation and other key cellular processes. Here we present a genome-wide chromatin landscape for Drosophila melanogaster based on eighteen histone modifications, summarized by nine prevalent combinatorial patterns. Integrative analysis with other data (non-histone chromatin proteins, DNase I hypersensitivity, GRO-Seq reads produced by engaged polymerase, short/long RNA products) reveals discrete characteristics of chromosomes, genes, regulatory elements and other functional domains. We find that active genes display distinct chromatin signatures that are correlated with disparate gene lengths, exon patterns, regulatory functions and genomic contexts. We also demonstrate a diversity of signatures among Polycomb targets that include a subset with paused polymerase. This systematic profiling and integrative analysis of chromatin signatures provides insights into how genomic elements are regulated, and will serve as a resource for future experimental investigations of genome structure and function.

Published
2011

13. SGN-B7H4V, an investigational vedotin ADC directed to the immune checkpoint ligand B7-H4, shows promising activity in preclinical models

Author

Gray, Elizabeth, primary, Ulrich, Michelle, additional, Epp, Angela, additional, Younan, Patrick, additional, Sahetya, Disha, additional, Hensley, Kelly, additional, Allred, Sean, additional, Huang, Li-Ya, additional, Hahn, Julie, additional, Gahnberg, Kristen, additional, Treuting, Piper M, additional, Trueblood, Esther S, additional, Gosink, John J, additional, Thurman, Robert, additional, Wo, Serena, additional, Spahr, Kellie, additional, Haass, Evgenia Jane, additional, Snead, Katie, additional, Miller, Dannah, additional, Padilla, Mary, additional, Smith, Alyson J, additional, Frantz, Chris, additional, Schrum, Jason P, additional, Nazarenko, Natalya, additional, and Gardai, Shyra J, additional

Published
2023
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14. Brentuximab Vedotin-Driven Microtubule Disruption Results in Endoplasmic Reticulum Stress Leading to Immunogenic Cell Death and Antitumor Immunity

Author

Heiser, Ryan A., primary, Cao, Anthony T., additional, Zeng, Weiping, additional, Ulrich, Michelle, additional, Younan, Patrick, additional, Anderson, Martha E., additional, Trueblood, Esther S., additional, Jonas, Mechthild, additional, Thurman, Robert, additional, Law, Che-Leung, additional, and Gardai, Shyra J., additional

Published
2023
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15. HER2-Selective and Reversible Tyrosine Kinase Inhibitor Tucatinib Potentiates the Activity of T-DM1 in Preclinical Models of HER2-positive Breast Cancer

Author

Olson, Devra, primary, Taylor, Janelle, additional, Willis, Kelsi, additional, Hensley, Kelly, additional, Allred, Sean, additional, Zaval, Margo, additional, Farr, Lauren, additional, Thurman, Robert, additional, Jain, Nishi, additional, Hein, Renee, additional, Ulrich, Michelle, additional, Peterson, Scott, additional, and Kulukian, Anita, additional

Published
2023
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16. Figure S4 from HER2-Selective and Reversible Tyrosine Kinase Inhibitor Tucatinib Potentiates the Activity of T-DM1 in Preclinical Models of HER2-positive Breast Cancer

Author

Olson, Devra, primary, Taylor, Janelle, primary, Willis, Kelsi, primary, Hensley, Kelly, primary, Allred, Sean, primary, Zaval, Margo, primary, Farr, Lauren, primary, Thurman, Robert, primary, Jain, Nishi, primary, Hein, Renee, primary, Ulrich, Michelle, primary, Peterson, Scott, primary, and Kulukian, Anita, primary

Published
2023
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17. Supplementary Materials and Methods from HER2-Selective and Reversible Tyrosine Kinase Inhibitor Tucatinib Potentiates the Activity of T-DM1 in Preclinical Models of HER2-positive Breast Cancer

Author

Olson, Devra, primary, Taylor, Janelle, primary, Willis, Kelsi, primary, Hensley, Kelly, primary, Allred, Sean, primary, Zaval, Margo, primary, Farr, Lauren, primary, Thurman, Robert, primary, Jain, Nishi, primary, Hein, Renee, primary, Ulrich, Michelle, primary, Peterson, Scott, primary, and Kulukian, Anita, primary

Published
2023
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18. Data from HER2-Selective and Reversible Tyrosine Kinase Inhibitor Tucatinib Potentiates the Activity of T-DM1 in Preclinical Models of HER2-positive Breast Cancer

Author

Olson, Devra, primary, Taylor, Janelle, primary, Willis, Kelsi, primary, Hensley, Kelly, primary, Allred, Sean, primary, Zaval, Margo, primary, Farr, Lauren, primary, Thurman, Robert, primary, Jain, Nishi, primary, Hein, Renee, primary, Ulrich, Michelle, primary, Peterson, Scott, primary, and Kulukian, Anita, primary

Published
2023
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21. Supplementary Methods from SGN-CD228A Is an Investigational CD228-Directed Antibody–Drug Conjugate with Potent Antitumor Activity across a Wide Spectrum of Preclinical Solid Tumor Models

Author

Mazahreh, Rebecca, primary, Mason, Marsha L., primary, Gosink, John J., primary, Olson, Devra J., primary, Thurman, Robert, primary, Hale, Christopher, primary, Westendorf, Lori, primary, Pires, Thomas A., primary, Leiske, Christopher I., primary, Carlson, Markus, primary, Nguyen, Liem T., primary, Cochran, Julia H., primary, Okeley, Nicole M., primary, Yumul, Roma, primary, Jin, Steven, primary, Stone, Ivan J., primary, Sahetya, Disha, primary, Nesterova, Albina, primary, Allred, Sean, primary, Hensley, Kelly M., primary, Hu, Rachael, primary, Lawrence, Robert, primary, Lewis, Timothy S., primary, and Sandall, Sharsti, primary

Published
2023
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22. Data from SGN-CD228A Is an Investigational CD228-Directed Antibody–Drug Conjugate with Potent Antitumor Activity across a Wide Spectrum of Preclinical Solid Tumor Models

Author

Mazahreh, Rebecca, primary, Mason, Marsha L., primary, Gosink, John J., primary, Olson, Devra J., primary, Thurman, Robert, primary, Hale, Christopher, primary, Westendorf, Lori, primary, Pires, Thomas A., primary, Leiske, Christopher I., primary, Carlson, Markus, primary, Nguyen, Liem T., primary, Cochran, Julia H., primary, Okeley, Nicole M., primary, Yumul, Roma, primary, Jin, Steven, primary, Stone, Ivan J., primary, Sahetya, Disha, primary, Nesterova, Albina, primary, Allred, Sean, primary, Hensley, Kelly M., primary, Hu, Rachael, primary, Lawrence, Robert, primary, Lewis, Timothy S., primary, and Sandall, Sharsti, primary

Published
2023
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23. Supplementary Figures from SGN-CD228A Is an Investigational CD228-Directed Antibody–Drug Conjugate with Potent Antitumor Activity across a Wide Spectrum of Preclinical Solid Tumor Models

Author

Mazahreh, Rebecca, primary, Mason, Marsha L., primary, Gosink, John J., primary, Olson, Devra J., primary, Thurman, Robert, primary, Hale, Christopher, primary, Westendorf, Lori, primary, Pires, Thomas A., primary, Leiske, Christopher I., primary, Carlson, Markus, primary, Nguyen, Liem T., primary, Cochran, Julia H., primary, Okeley, Nicole M., primary, Yumul, Roma, primary, Jin, Steven, primary, Stone, Ivan J., primary, Sahetya, Disha, primary, Nesterova, Albina, primary, Allred, Sean, primary, Hensley, Kelly M., primary, Hu, Rachael, primary, Lawrence, Robert, primary, Lewis, Timothy S., primary, and Sandall, Sharsti, primary

Published
2023
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24. Supplementary Tables from SGN-CD228A Is an Investigational CD228-Directed Antibody–Drug Conjugate with Potent Antitumor Activity across a Wide Spectrum of Preclinical Solid Tumor Models

Author

Mazahreh, Rebecca, primary, Mason, Marsha L., primary, Gosink, John J., primary, Olson, Devra J., primary, Thurman, Robert, primary, Hale, Christopher, primary, Westendorf, Lori, primary, Pires, Thomas A., primary, Leiske, Christopher I., primary, Carlson, Markus, primary, Nguyen, Liem T., primary, Cochran, Julia H., primary, Okeley, Nicole M., primary, Yumul, Roma, primary, Jin, Steven, primary, Stone, Ivan J., primary, Sahetya, Disha, primary, Nesterova, Albina, primary, Allred, Sean, primary, Hensley, Kelly M., primary, Hu, Rachael, primary, Lawrence, Robert, primary, Lewis, Timothy S., primary, and Sandall, Sharsti, primary

Published
2023
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26. SGN-CD228A is an investigational CD228-directed antibody-drug conjugate with potent antitumor activity across a wide spectrum of preclinical solid tumor models

Author

Mazahreh, Rebecca, primary, Mason, Marsha L., additional, Gosink, John J., additional, Olson, Devra J., additional, Thurman, Robert, additional, Hale, Christopher, additional, Westendorf, Lori, additional, Pires, Thomas A., additional, Leiske, Christopher I., additional, Carlson, Markus, additional, Nguyen, Liem T., additional, Cochran, Julia H., additional, Okeley, Nicole M., additional, Yumul, Roma, additional, Jin, Steven, additional, Stone, Ivan J., additional, Sahetya, Disha, additional, Nesterova, Albina, additional, Allred, Sean, additional, Hensley, Kelly M., additional, Hu, Rachael, additional, Lawrence, Robert, additional, Lewis, Timothy S., additional, and Sandall, Sharsti, additional

Published
2023
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27. Mapping and Dynamics of Regulatory DNA and Transcription Factor Networks in A. thaliana

Author

Sullivan, Alessandra M., Arsovski, Andrej A., Lempe, Janne, Bubb, Kerry L., Weirauch, Matthew T., Sabo, Peter J., Sandstrom, Richard, Thurman, Robert E., Neph, Shane, Reynolds, Alex P., Stergachis, Andrew B., Vernot, Benjamin, Johnson, Audra K., Haugen, Eric, Sullivan, Shawn T., Thompson, Agnieszka, Neri, Fidencio V., III, Weaver, Molly, Diegel, Morgan, Mnaimneh, Sanie, Yang, Ally, Hughes, Timothy R., Nemhauser, Jennifer L., Queitsch, Christine, and Stamatoyannopoulos, John A.

Published
2014
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30. Meditation and Education: India, Tibet, and Modern America

Author

Thurman, Robert A. F.

Abstract

This article explores Asian traditions of meditation, with particular attention to Buddhism as it was developed in ancient India. It delineates a core curriculum, initially developed in monastic institutions of higher education, that has been most fully preserved in Tibet. It then explores how this curriculum might be adapted so that it can help support a genuinely humanistic education within American higher education. This exploration focuses not only on the inherent values of Buddhist meditation but also on practical strategies that can be used to introduce these values in the academic curriculum and in the broader campus life.

Published
2006
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31. Cell-of-origin chromatin organization shapes the mutational landscape of cancer

Author

Polak, Paz, Karlic, Rosa, Koren, Amnon, Thurman, Robert, Sandstrom, Richard, Lawrence, Michael S., Reynolds, Alex, Rynes, Eric, Vlahovicek, Kristian, Stamatoyannopoulos, John A., and Sunyaev, Shamil R.

Subjects
Gene mutations -- Research, Chromatin -- Health aspects, Genetic research, Cancer -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Cancer is a disease potentiated by mutations in somatic cells. Cancer mutations are not distributed uniformly along the human genome. Instead, different human genomic regions vary by up to fivefold in the local density of cancer somatic mutations (1), posing a fundamental problem for statistical methods used in cancer genomics. Epigenomic organization has been proposed as a major determinant of the cancer mutational landscape (1-5). However, both somatic mutagenesis and epigenomic features are highly cell-type-specific (6,7). We investigated the distribution of mutations in multiple independent samples of diverse cancer types and compared them to cell-type-specific epigenomic features. Here we show that chromatin accessibility and modification, together with replication timing, explain up to 86% of the variance in mutation rates along cancer genomes. The best predictors of local somatic mutation density are epigenomic features derived from the most likely cell type of origin of the corresponding malignancy. Moreover, we find that cell-of-origin chromatin features are much stronger determinants of cancer mutation profiles than chromatin features of matched cancer cell lines. Furthermore, we show that the cell type of origin of a cancer can be accurately determined based on the distribution of mutations along its genome. Thus, the DNA sequence of a cancer genome encompasses a wealth of information about the identity and epigenomic features of its cell of origin., Recent studies have begun to address the underlying causes of cancer mutational heterogeneity by comparing mutation rate variation to the distribution of sequence features, gene expression and epigenetic marks along [...]

Published
2015

32. Systematic Localization of Common Disease-Associated Variation in Regulatory DNA

Author

Maurano, Matthew T., Humbert, Richard, Rynes, Eric, Thurman, Robert E., Haugen, Eric, Wang, Hao, Reynolds, Alex P., Sandstrom, Richard, Qu, Hongzhu, Brody, Jennifer, Shafer, Anthony, Neri, Fidencio, Lee, Kristen, Kutyavin, Tanya, Stehling-Sun, Sandra, Johnson, Audra K., Canfield, Theresa K., Giste, Erika, Diegel, Morgan, Bates, Daniel, Hansen, R. Scott, Neph, Shane, Sabo, Peter J., Heimfeld, Shelly, Raubitschek, Antony, Ziegler, Steven, Cotsapas, Chris, Sotoodehnia, Nona, Glass, Ian, Sunyaev, Shamil R., Kaul, Rajinder, and Stamatoyannopoulos, John A.

Published
2012
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33. Abstract 1281: SGN-B7H4V shows immunomodulatory activity through induction of immunogenic cell death

Author

Gray, Elizabeth E., primary, Ulrich, Michelle, additional, Epp, Angela, additional, Younan, Patrick, additional, Hensley, Kelly, additional, Allred, Sean, additional, Hahn, Julie, additional, Gahnberg, Kristen, additional, Treuting, Piper M., additional, Gosink, John J., additional, Thurman, Robert, additional, Smith, Alyson J., additional, Schrum, Jason, additional, Nazarenko, Natalya, additional, and Gardai, Shyra J., additional

Published
2022
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35. Flexibility in Program Planning and NCATE Standards.

Author

ERIC Clearinghouse on Teacher Education, Washington, DC. and Thurman, Robert

Abstract

This monograph discusses the question of flexibility as permitted by the standards of the National Council of Accreditation of Teacher Education (NCATE), a question of concern to educators eager to meet the standards and to satisfy the needs of school personnel. Flexibility is defined, and the purpose and design of NCATE standards discussed. Thurman indicates that deliberate effort has been made in the standards to encourage individuality, imagination, and innovation. In spite of this, he continues, questions about flexibility persist for the following reasons: a) lack of distinction between flexibility and alternative approaches, b) lack of distinction between standards as a basis for program development and evaluation and as a framework for preparing the institutional report, c) lack of statements in the standards about experimentation, and d) uncertainty about what the visiting team and evaluation board deem important. Each of these reasons is examined in relation to the standards. Thurman advocates working within the standards to improve and develop programs and further explication of the standards by NCATE. (JA)

Published
1974

36. Topologically associating domains are stable units of replication-timing regulation

Author

Pope, Benjamin D., Ryba, Tyrone, Dileep, Vishnu, Yue, Feng, Wu, Weisheng, Denas, Olgert, Vera, Daniel L., Wang, Yanli, Hansen, R. Scott, Canfield, Theresa K., Thurman, Robert E., Cheng, Yong, Gulsoy, Gunhan, Dennis, Jonathan H., Snyder, Michael P., Stamatoyannopoulos, John A., Taylor, James, Hardison, Ross C., Kahveci, Tamer, Ren, Bing, and Gilbert, David M.

Subjects
Genetic research, Genetic regulation -- Research, Chromosome replication -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Benjamin D. Pope [1]; Tyrone Ryba [2]; Vishnu Dileep [1]; Feng Yue [3, 4]; Weisheng Wu [5]; Olgert Denas [6]; Daniel L. Vera [1]; Yanli Wang [4]; R. Scott [...]

Published
2014
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37. A comparative encyclopedia of DNA elements in the mouse genome

Author

Yue, Feng, Cheng, Yong, Breschi, Alessandra, Vierstra, Jeff, Wu, Weisheng, Ryba, Tyrone, Sandstrom, Richard, Ma, Zhihai, Davis, Carrie, Pope, Benjamin D., Shen, Yin, Pervouchine, Dmitri D., Djebali, Sarah, Thurman, Robert E., Kaul, Rajinder, Rynes, Eric, Kirilusha, Anthony, Marinov, Georgi K., Williams, Brian A., Trout, Diane, Amrhein, Henry, Fisher-Aylor, Katherine, Antoshechkin, Igor, DeSalvo, Gilberto, See, Lei-Hoon, Fastuca, Meagan, Drenkow, Jorg, Zaleski, Chris, Dobin, Alex, Prieto, Pablo, Lagarde, Julien, Bussotti, Giovanni, Tanzer, Andrea, Denas, Olgert, Li, Kanwei, Bender, M. A., Zhang, Miaohua, Byron, Rachel, Groudine, Mark T., McCleary, David, Pham, Long, Ye, Zhen, Kuan, Samantha, Edsall, Lee, Wu, Yi-Chieh, Rasmussen, Matthew D., Bansal, Mukul S., Kellis, Manolis, Keller, Cheryl A., Morrissey, Christapher S., Mishra, Tejaswini, Jain, Deepti, Dogan, Nergiz, Harris, Robert S., Cayting, Philip, Kawli, Trupti, Boyle, Alan P., Euskirchen, Ghia, Kundaje, Anshul, Lin, Shin, Lin, Yiing, Jansen, Camden, Malladi, Venkat S., Cline, Melissa S., Erickson, Drew T., Kirkup, Vanessa M., Learned, Katrina, Sloan, Cricket A., Rosenbloom, Kate R., Lacerda de Sousa, Beatriz, Beal, Kathryn, Pignatelli, Miguel, Flicek, Paul, Lian, Jin, Kahveci, Tamer, Lee, Dongwon, James Kent, W., Ramalho Santos, Miguel, Herrero, Javier, Notredame, Cedric, Johnson, Audra, Vong, Shinny, Lee, Kristen, Bates, Daniel, Neri, Fidencio, Diegel, Morgan, Canfield, Theresa, Sabo, Peter J., Wilken, Matthew S., Reh, Thomas A., Giste, Erika, Shafer, Anthony, Kutyavin, Tanya, Haugen, Eric, Dunn, Douglas, Reynolds, Alex P., Neph, Shane, Humbert, Richard, Scott Hansen, R., De Bruijn, Marella, Selleri, Licia, Rudensky, Alexander, Josefowicz, Steven, Samstein, Robert, Eichler, Evan E., Orkin, Stuart H., Levasseur, Dana, Papayannopoulou, Thalia, Chang, Kai-Hsin, Skoultchi, Arthur, Gosh, Srikanta, Disteche, Christine, Treuting, Piper, Wang, Yanli, Weiss, Mitchell J., Blobel, Gerd A., Cao, Xiaoyi, Zhong, Sheng, Wang, Ting, Good, Peter J., Lowdon, Rebecca F., Adams, Leslie B., Zhou, Xiao-Qiao, Pazin, Michael J., Feingold, Elise A., Wold, Barbara, Taylor, James, Mortazavi, Ali, Weissman, Sherman M., Stamatoyannopoulos, John A., Snyder, Michael P., Guigo, Roderic, Gingeras, Thomas R., Gilbert, David M., Hardison, Ross C., Beer, Michael A., and Ren, Bing

Subjects
Man -- Genetic aspects, Genetic research, Human beings -- Genetic aspects, Genomes -- Comparative analysis, Mice -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The laboratory mouse shares the majority of its protein-coding genes with humans, making it the premier model organism in biomedical research, yet the two mammals differ in significant ways. To gain greater insights into both shared and species-specific transcriptional and cellular regulatory programs in the mouse, the Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types. By comparing with the human genome, we not only confirm substantial conservation in the newly annotated potential functional sequences, but also find a large degree of divergence of sequences involved in transcriptional regulation, chromatin state and higher order chromatin organization. Our results illuminate the wide range of evolutionary forces acting on genes and their regulatory regions, and provide a general resource for research into mammalian biology and mechanisms of human diseases., Author(s): Feng Yue [1, 2]; Yong Cheng [3]; Alessandra Breschi [4]; Jeff Vierstra [5]; Weisheng Wu [6]; Tyrone Ryba [7]; Richard Sandstrom [5]; Zhihai Ma [3]; Carrie Davis [8]; Benjamin [...]

Published
2014
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38. Conservation of trans-acting circuitry during mammalian regulatory evolution

Author

Stergachis, Andrew B., Neph, Shane, Sandstrom, Richard, Haugen, Eric, Reynolds, Alex P., Zhang, Miaohua, Byron, Rachel, Canfield, Theresa, Stelhing-Sun, Sandra, Lee, Kristen, Thurman, Robert E., Vong, Shinny, Bates, Daniel, Neri, Fidencio, Diegel, Morgan, Giste, Erika, Dunn, Douglas, Vierstra, Jeff, Hansen, R. Scott, Johnson, Audra K., Sabo, Peter J., Wilken, Matthew S., Reh, Thomas A., Treuting, Piper M., Kaul, Rajinder, Groudine, Mark, Bender, M. A., Borenstein, Elhanan, and Stamatoyannopoulos, John A.

Subjects
Evolution -- Genetic aspects, Genetic regulation -- Methods, Mammals -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The basic body plan and major physiological axes have been highly conserved during mammalian evolution, yet only a small fraction of the human genome sequence appears to be subject to evolutionary constraint. To quantify cis- versus trans-acting contributions to mammalian regulatory evolution, we performed genomic DNase I footprinting of the mouse genome across 25 cell and tissue types, collectively defining [similar]8.6 million transcription factor (TF) occupancy sites at nucleotide resolution. Here we show that mouse TF footprints conjointly encode a regulatory lexicon that is [similar]95% similar with that derived from human TF footprints. However, only [similar]20% of mouse TF footprints have human orthologues. Despite substantial turnover of the cis-regulatory landscape, nearly half of all pairwise regulatory interactions connecting mouse TF genes have been maintained in orthologous human cell types through evolutionary innovation of TF recognition sequences. Furthermore, the higher-level organization of mouse TF-to-TF connections into cellular network architectures is nearly identical with human. Our results indicate that evolutionary selection on mammalian gene regulation is targeted chiefly at the level of trans-regulatory circuitry, enabling and potentiating cis-regulatory plasticity., Author(s): Andrew B. Stergachis [1]; Shane Neph [1]; Richard Sandstrom [1]; Eric Haugen [1]; Alex P. Reynolds [1]; Miaohua Zhang [2]; Rachel Byron [2]; Theresa Canfield [1]; Sandra Stelhing-Sun [1]; [...]

Published
2014
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39. Domains of genome-wide gene expression dysregulation in Down's syndrome

Author

Letourneau, Audrey, Santoni, Federico A., Bonilla, Ximena, Sailani, M. Reza, Gonzalez, David, Kind, Jop, Chevalier, Claire, Thurman, Robert, Sandstorm, Richard S., Hibaoui, Youssef, Garieri, Marco, Popadin, Konstatin, Falconnet, Emilie, Gagnebin, Maryline, Gehrig, Corinne, Vannier, Anne, and Guipponi, Michael

Subjects
Gene expression -- Health aspects, Down syndrome -- Genetic aspects, Genetic regulation -- Health aspects, Genome-wide association studies, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Trisomy 21 is the most frequent genetic cause of cognitive impairment. To assess the perturbations of gene expression in trisomy 21, and to eliminate the noise of genomic variability, we studied the transcriptome of fetal fibroblasts from a pair of monozygotic twins discordant for trisomy 21. Here we show that the differential expression between the twins is organized in domains along all chromosomes that are either upregulated or downregulated. These gene expression dysregulation domains (GEDDs) can be defined by the expression level of their gene content, and are well conserved in induced pluripotent stem cells derived from the twins' fibroblasts. Comparison of the transcriptome of the Ts65Dn mouse model of Down's syndrome and normal littermate mouse fibroblasts also showed GEDDs along the mouse chromosomes that were syntenic in human. The GEDDs correlate with the lamina-associated (LADs) and replication domains of mammalian cells. The overall position of LADs was not altered in trisomic cells; however, the H3K4me3 profile of the trisomic fibroblasts was modified and accurately followed the GEDD pattern. These results indicate that the nuclear compartments of trisomic cells undergo modifications of the chromatin environment influencing the overall transcriptome, and that GEDDs may therefore contribute to some trisomy 21 phenotypes. By studying the transcriptome of fetal cells of monozygotic twins discordant for trisomy 21, this paper finds that differential expression between the twins is organized in domains along all chromosomes; these gene expression dysregulation domains are conserved in the mouse model of Down's syndrome and correlate with the lamina-associated domains and replication domains. The genetic landscape of Down's syndrome Down's syndrome is thought to be caused by gene expression disturbances, so to understand the molecular mechanisms that underlie the phenotype requires an understanding of the transcriptome differences in cells and tissues carrying the total or partial trisomy of chromosome 21 that is typical of the condition. This study of the transcriptome of fetal cells of monozygotic twins discordant for trisomy 21 shows that differential expression between the twins is organized in domains along all chromosomes. These gene expression dysregulation domains are conserved in the mouse model of Down's syndrome and correlate with the lamina-associated domains and replication domains. Although the overall genome topology is not altered in trisomic cells, the authors report modifications of the chromatin environment influencing the overall transcriptome and suggest that the dysregulation domains they identify may therefore contribute to some Down's syndrome phenotypes., Author(s): Audrey Letourneau [sup.1] , Federico A. Santoni [sup.1] , Ximena Bonilla [sup.1] , M. Reza Sailani [sup.1] , David Gonzalez [sup.2] , Jop Kind [sup.3] , Claire Chevalier [sup.4] [...]

Published
2014
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41. Integrative analysis of 111 reference human epigenomes

Author

Consortium, Roadmap Epigenomics, Kundaje, Anshul, Meuleman, Wouter, Ernst, Jason, Bilenky, Misha, Yen, Angela, Heravi-Moussavi, Alireza, Kheradpour, Pouya, Zhang, Zhizhuo, Wang, Jianrong, Ziller, Michael J., Whitaker, John W., Ward, Lucas D., Sarkar, Abhishek, Sandstrom, Richard S., Wu, Yi-Chieh, Pfenning, Andreas R., Wang, Xinchen, Claussnitzer, Melina, Liu, Yaping, Harris, Alan R., Epstein, Charles B., Leung, Danny, Hawkins, David R., Hong, Chibo, Mungall, Andrew J., Chuah, Eric, Hansen, Scott R., Bansal, Mukul S., Dixon, Jesse R., Feizi, Soheil, Kim, Ah-Ram, Li, Daofeng, Elliott, GiNell, Neph, Shane J., Polak, Paz, Ray, Pradipta, Siebenthall, Kyle T., Thurman, Robert E., Zhou, Xin, Boyer, Laurie A., De Jager, Philip L., Fisher, Susan J., Li, Wei, McManus, Michael T., Sunyaev, Shamil, Tlsty, Thea D., Wang, Wei, Waterland, Robert A., Costello, Joseph F., Hirst, Martin, Stamatoyannopoulos, John A., Wang, Ting, Amin, Viren, Schultz, Matthew D., Quon, Gerald, Eaton, Matthew L., Pfenning, Andreas, Liu, Melina ClaussnitzerYaping, Coarfa, Cristian, Shoresh, Noam, Gjoneska, Elizabeta, Xie, Wei, Lister, Ryan, Moore, Richard, Tam, Angela, Canfield, Theresa K., Kaul, Rajinder, Sabo, Peter J., Carles, Annaick, Farh, Kai-How, Karlic, Rosa, Kulkarni, Ashwinikumar, Lowdon, Rebecca, Mercer, Tim R., Onuchic, Vitor, Rajagopal, Nisha, Sallari, Richard C., Sinnott-Armstrong, Nicholas A., Stevens, Michael, Wu, Jie, Zhang, Bo, Abdennur, Nezar, Adli, Mazhar, Akerman, Martin, Barrera, Luis, Antosiewicz-Bourget, Jessica, Ballinger, Tracy, Barnes, Michael J., Bates, Daniel, Bell, Robert J. A., Bennett, David A., Bianco, Katherine, Bock, Christoph, Boyle, Patrick, Brinchmann, Jan, Caballero-Campo, Pedro, Camahort, Raymond, Carrasco-Alfonso, Marlene J., Charnecki, Timothy, Chen, Huaming, Chen, Zhao, Cheng, Jeffrey B., Cho, Stephanie, Chu, Andy, Chung, Wen-Yu, Cowan, Chad, Deng, Qixia Athena, Deshpande, Vikram, Diegel, Morgan, Ding, Bo, Durham, Timothy, Echipare, Lorigail, Edsall, Lee, Flowers, David, Genbacev-Krtolica, Olga, Gifford, Casey, Gillespie, Shawn, Giste, Erika, Glass, Ian A., Gnirke, Andreas, Gormley, Matthew, Gu, Hongcang, Gu, Junchen, Hafler, David A., Hangauer, Matthew J., Hariharan, Manoj, Hatan, Meital, Haugen, Eric, He, Yupeng, Heimfeld, Shelly, Herlofsen, Sarah, Hou, Zhonggang, Humbert, Richard, Issner, Robbyn, Jackson, Andrew R., Jia, Haiyang, Jiang, Peng, Johnson, Audra K., Kadlecek, Theresa, Kamoh, Baljit, Kapidzic, Mirhan, Kent, Jim, Kim, Audrey, Kleinewietfeld, Markus, Klugman, Sarit, Krishnan, Jayanth, Kuan, Samantha, Kutyavin, Tanya, Lee, Ah-Young, Lee, Kristen, Li, Jian, Li, Nan, Li, Yan, Ligon, Keith L., Lin, Shin, Lin, Yiing, Liu, Jie, Liu, Yuxuan, Luckey, John C., Ma, Yussanne P., Maire, Cecile, Marson, Alexander, Mattick, John S., Mayo, Michael, McMaster, Michael, Metsky, Hayden, Mikkelsen, Tarjei, Miller, Diane, Miri, Mohammad, Mukame, Eran, Nagarajan, Raman P., Neri, Fidencio, Nery, Joseph, Nguyen, Tung, OʼGeen, Henriette, Paithankar, Sameer, Papayannopoulou, Thalia, Pelizzola, Mattia, Plettner, Patrick, Propson, Nicholas E., Raghuraman, Sriram, Raney, Brian J., Raubitschek, Anthony, Reynolds, Alex P., Richards, Hunter, Riehle, Kevin, Rinaudo, Paolo, Robinson, Joshua F., Rockweiler, Nicole B., Rosen, Evan, Rynes, Eric, Schein, Jacqueline, Sears, Renee, Sejnowski, Terrence, Shafer, Anthony, Shen, Li, Shoemaker, Robert, Sigaroudinia, Mahvash, Slukvin, Igor, Stehling-Sun, Sandra, Stewart, Ron, Subramanian, Sai Lakshmi, Suknuntha, Kran, Swanson, Scott, Tian, Shulan, Tilden, Hannah, Tsai, Linus, Urich, Mark, Vaughn, Ian, Vierstra, Jeff, Vong, Shinny, Wagner, Ulrich, Wang, Hao, Wang, Tao, Wang, Yunfei, Weiss, Arthur, Whitton, Holly, Wildberg, Andre, Witt, Heather, Won, Kyoung-Jae, Xie, Mingchao, Xing, Xiaoyun, Xu, Iris, Xuan, Zhenyu, Ye, Zhen, Yen, Chia-an, Yu, Pengzhi, Zhang, Xian, Zhang, Xiaolan, Zhao, Jianxin, Zhou, Yan, Zhu, Jiang, Zhu, Yun, Ziegler, Steven, Beaudet, Arthur E., Farnham, Peggy J., Haussler, David, Jones, Steven J. M., Marra, Marco A., Thomson, James A., Tsai, Li-Huei, Zhang, Michael Q., Chadwick, Lisa H., Bernstein, Bradley E., Ecker, Joseph R., Meissner, Alexander, Milosavljevic, Aleksandar, Ren, Bing, and Kellis, Manolis

Published
2015
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43. An integrated encyclopedia of DNA elements in the human genome

Author

Dunham, Ian, Kundaje, Anshul, Aldred, Shelley F., Collins, Patrick J., Davis, Carrie A., Doyle, Francis, Epstein, Charles B., Frietze, Seth, Harrow, Jennifer, Kaul, Rajinder, Khatun, Jainab, Lajoie, Bryan R., Landt, Stephen G., Lee, Bum-Kyu, Pauli, Florencia, Rosenbloom, Kate R., Sabo, Peter, Safi, Alexias, Sanyal, Amartya, Shoresh, Noam, Simon, Jeremy M., Song, Lingyun, Trinklein, Nathan D., Altshuler, Robert C., Birney, Ewan, Brown, James B., Cheng, Chao, Djebali, Sarah, Dong, Xianjun, Ernst, Jason, Furey, Terrence S., Gerstein, Mark, Giardine, Belinda, Greven, Melissa, Hardison, Ross C., Harris, Robert S., Herrero, Javier, Hoffman, Michael M., Iyer, Sowmya, Kellis, Manolis, Kheradpour, Pouya, Lassmann, Timo, Li, Qunhua, Lin, Xinying, Marinov, Georgi K., Merkel, Angelika, Mortazavi, Ali, Parker, Stephen C. J., Reddy, Timothy E., Rozowsky, Joel, Schlesinger, Felix, Thurman, Robert E., Wang, Jie, Ward, Lucas D., Whitfield, Troy W., Wilder, Steven P., Wu, Weisheng, Xi, Hualin S., Yip, Kevin Y., Zhuang, Jiali, Bernstein, Bradley E., Green, Eric D., Gunter, Chris, Snyder, Michael, Pazin, Michael J., Lowdon, Rebecca F., Dillon, Laura A. L., Adams, Leslie B., Kelly, Caroline J., Zhang, Julia, Wexler, Judith R., Good, Peter J., Feingold, Elise A., Crawford, Gregory E., Dekker, Job, Elnitski, Laura, Farnham, Peggy J., Giddings, Morgan C., Gingeras, Thomas R., Guigo, Roderic, Hubbard, Timothy J., Kent, W. James, Lieb, Jason D., Margulies, Elliott H., Myers, Richard M., Stamatoyannopoulos, John A., Tenenbaum, Scott A., Weng, Zhiping, White, Kevin P., Wold, Barbara, Yu, Yanbao, Wrobel, John, Risk, Brian A., Gunawardena, Harsha P., Kuiper, Heather C., Maier, Christopher W., Xie, Ling, Chen, Xian, Mikkelsen, Tarjei S., Gillespie, Shawn, Goren, Alon, Ram, Oren, Zhang, Xiaolan, Wang, Li, Issner, Robbyn, Coyne, Michael J., Durham, Timothy, Ku, Manching, Truong, Thanh, Eaton, Matthew L., Dobin, Alex, Tanzer, Andrea, Lagarde, Julien, Lin, Wei, Xue, Chenghai, Williams, Brian A., Zaleski, Chris, Roder, Maik, Kokocinski, Felix, Abdelhamid, Rehab F., Alioto, Tyler, Antoshechkin, Igor, Baer, Michael T., Batut, Philippe, Bell, Ian, Bell, Kimberly, Chakrabortty, Sudipto, Chrast, Jacqueline, Curado, Joao, Derrien, Thomas, Drenkow, Jorg, Dumais, Erica, Dumais, Jackie, Duttagupta, Radha, Fastuca, Megan, Fejes-Toth, Kata, Ferreira, Pedro, Foissac, Sylvain, Fullwood, Melissa J., Gao, Hui, Gonzalez, David, Gordon, Assaf, Howald, Cedric, Jha, Sonali, Johnson, Rory, Kapranov, Philipp, King, Brandon, Kingswood, Colin, Li, Guoliang, Luo, Oscar J., Park, Eddie, Preall, Jonathan B., Presaud, Kimberly, Ribeca, Paolo, Robyr, Daniel, Ruan, Xiaoan, Sammeth, Michael, Sandhu, Kuljeet Singh, Schaeffer, Lorain, See, Lei-Hoon, Shahab, Atif, Skancke, Jorgen, Suzuki, Ana Maria, Takahashi, Hazuki, Tilgner, Hagen, Trout, Diane, Walters, Nathalie, Wang, Huaien, Hayashizaki, Yoshihide, Reymond, Alexandre, Antonarakis, Stylianos E., Hannon, Gregory J., Ruan, Yijun, Carninci, Piero, Sloan, Cricket A., Learned, Katrina, Malladi, Venkat S., Wong, Matthew C., Barber, Galt P., Cline, Melissa S., Dreszer, Timothy R., Heitner, Steven G., Karolchik, Donna, Kirkup, Vanessa M., Meyer, Laurence R., Long, Jeffrey C., Maddren, Morgan, Raney, Brian J., Grasfeder, Linda L., Giresi, Paul G., Battenhouse, Anna, Sheffield, Nathan C., Showers, Kimberly A., London, Darin, Bhinge, Akshay A., Shestak, Christopher, Schaner, Matthew R., Ki Kim, Seul, Zhang, Zhuzhu Z., Mieczkowski, Piotr A., Mieczkowska, Joanna O., Liu, Zheng, McDaniell, Ryan M., Ni, Yunyun, Rashid, Naim U., Kim, Min Jae, Adar, Sheera, Zhang, Zhancheng, Wang, Tianyuan, Winter, Deborah, Keefe, Damian, Iyer, Vishwanath R., Zheng, Meizhen, Wang, Ping, Gertz, Jason, Vielmetter, Jost, Partridge, E., Varley, Katherine E., Gasper, Clarke, Bansal, Anita, Pepke, Shirley, Jain, Preti, Amrhein, Henry, Bowling, Kevin M., Anaya, Michael, Cross, Marie K., Muratet, Michael A., Newberry, Kimberly M., McCue, Kenneth, Nesmith, Amy S., Fisher-Aylor, Katherine I., Pusey, Barbara, DeSalvo, Gilberto, Parker, Stephanie L., Balasubramanian, Sreeram, Davis, Nicholas S., Meadows, Sarah K., Eggleston, Tracy, Newberry, J. Scott, Levy, Shawn E., Absher, Devin M., Wong, Wing H., Blow, Matthew J., Visel, Axel, Pennachio, Len A., Petrykowska, Hanna M., Abyzov, Alexej, Aken, Bronwen, Barrell, Daniel, Barson, Gemma, Berry, Andrew, Bignell, Alexandra, Boychenko, Veronika, Bussotti, Giovanni, Davidson, Claire, Despacio-Reyes, Gloria, Diekhans, Mark, Ezkurdia, Iakes, Frankish, Adam, Gilbert, James, Gonzalez, Jose Manuel, Griffiths, Ed, Harte, Rachel, Hendrix, David A., Hunt, Toby, Jungreis, Irwin, Kay, Mike, Khurana, Ekta, Leng, Jing, Lin, Michael F., Loveland, Jane, Lu, Zhi, Manthravadi, Deepa, Mariotti, Marco, Mudge, Jonathan, Mukherjee, Gaurab, Notredame, Cedric, Pei, Baikang, Rodriguez, Jose Manuel, Saunders, Gary, Sboner, Andrea, Searle, Stephen, Sisu, Cristina, Snow, Catherine, Steward, Charlie, Tapanari, Electra, Tress, Michael L., van Baren, Marijke J., Washietl, Stefan, Wilming, Laurens, Zadissa, Amonida, Zhang, Zhengdong, Brent, Michael, Haussler, David, Valencia, Alfonso, Addleman, Nick, Alexander, Roger P., Auerbach, Raymond K., Balasubramanian, Suganthi, Bettinger, Keith, Bhardwaj, Nitin, Boyle, Alan P., Cao, Alina R., Cayting, Philip, Charos, Alexandra, Cheng, Yong, Eastman, Catharine, Euskirchen, Ghia, Fleming, Joseph D., Grubert, Fabian, Habegger, Lukas, Hariharan, Manoj, Harmanci, Arif, Iyengar, Sushma, Jin, Victor X., Karczewski, Konrad J., Kasowski, Maya, Lacroute, Phil, Lam, Hugo, Lamarre-Vincent, Nathan, Lian, Jin, Lindahl-Allen, Marianne, Min, Renqiang, Miotto, Benoit, Monahan, Hannah, Moqtaderi, Zarmik, Mu, Xinmeng J., Ouyang, Zhengqing, Patacsil, Dorrelyn, Raha, Debasish, Ramirez, Lucia, Reed, Brian, Shi, Minyi, Slifer, Teri, Witt, Heather, Wu, Linfeng, Xu, Xiaoqin, Yan, Koon-Kiu, Yang, Xinqiong, Struhl, Kevin, Weissman, Sherman M., Penalva, Luiz O., Karmakar, Subhradip, Bhanvadia, Raj R., Choudhury, Alina, Domanus, Marc, Ma, Lijia, Moran, Jennifer, Victorsen, Alec, Auer, Thomas, Centanin, Lazaro, Eichenlaub, Michael, Gruhl, Franziska, Heermann, Stephan, Hoeckendorf, Burkhard, Inoue, Daigo, Kellner, Tanja, Kirchmaier, Stephan, Mueller, Claudia, Reinhardt, Robert, Schertel, Lea, Schneider, Stephanie, Sinn, Rebecca, Wittbrodt, Beate, Wittbrodt, Jochen, Partridge, E. Christopher, Jain, Gaurav, Balasundaram, Gayathri, Bates, Daniel L., Byron, Rachel, Canfield, Theresa K., Diegel, Morgan J., Dunn, Douglas, Ebersol, Abigail K., Frum, Tristan, Garg, Kavita, Gist, Erica, Hansen, R. Scott, Boatman, Lisa, Haugen, Eric, Humbert, Richard, Johnson, Audra K., Johnson, Ericka M., Kutyavin, Tattyana V., Lee, Kristen, Lotakis, Dimitra, Maurano, Matthew T., Neph, Shane J., Neri, Fiedencio V., Nguyen, Eric D., Qu, Hongzhu, Reynolds, Alex P., Roach, Vaughn, Rynes, Eric, Sanchez, Minerva E., Sandstrom, Richard S., Shafer, Anthony O., Stergachis, Andrew B., Thomas, Sean, Vernot, Benjamin, Vierstra, Jeff, Vong, Shinny, Weaver, Molly A., Yan, Yongqi, Zhang, Miaohua, Akey, Joshua M., Bender, Michael, Dorschner, Michael O., Groudine, Mark, MacCoss, Michael J., Navas, Patrick, Stamatoyannopoulos, George, Beal, Kathryn, Brazma, Alvis, Flicek, Paul, Johnson, Nathan, Lukk, Margus, Luscombe, Nicholas M., Sobral, Daniel, Vaquerizas, Juan M., Batzoglou, Serafim, Sidow, Arend, Hussami, Nadine, Kyriazopoulou-Panagiotopoulou, Sofia, Libbrecht, Max W., Schaub, Marc A., Miller, Webb, Bickel, Peter J., Banfai, Balazs, Boley, Nathan P., Huang, Haiyan, Li, Jingyi Jessica, Noble, William Stafford, Bilmes, Jeffrey A., Buske, Orion J., Sahu, Avinash D., Kharchenko, Peter V., Park, Peter J., Baker, Dannon, Taylor, James, and Lochovsky, Lucas

Subjects
Genetic research, Human genome -- Research, Genetic transcription -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research., Author(s): The ENCODE Project Consortium; Overall coordination (data analysis coordination); Ian Dunham [2]; Anshul Kundaje [3, 82]; Data production leads (data production); Shelley F. Aldred [4]; Patrick J. Collins [4]; [...]

Published
2012
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44. The accessible chromatin landscape of the human genome

Author

Thurman, Robert E., Rynes, Eric, Humbert, Richard, Vierstra, Jeff, Maurano, Matthew T., Haugen, Eric, Sheffield, Nathan C., Stergachis, Andrew B., Vernot, Benjamin, Garg, Kavita, John, Sam, Sandstrom, Richard, Bates, Daniel, Boatman, Lisa, Canfield, Theresa K., Diegel, Morgan, Dunn, Douglas, Ebersol, Abigail K., Frum, Tristan, Giste, Erika, Johnson, Audra K., Johnson, Ericka M., Kutyavin, Tanya, Lajoie, Bryan, Lee, Bum-Kyu, Lee, Kristen, London, Darin, Lotakis, Dimitra, Neph, Shane, Neri, Fidencio, Nguyen, Eric D., Qu, Hongzhu, Reynolds, Alex P., Roach, Vaughn, Safi, Alexias, Sanchez, Minerva E., Sanyal, Amartya, Shafer, Anthony, Simon, Jeremy M., Song, Lingyun, Vong, Shinny, Weaver, Molly, Yan, Yongqi, Zhang, Zhancheng, Zhang, Zhuzhu, Lenhard, Boris, Tewari, Muneesh, Dorschner, Michael O., Hansen, R. Scott, Navas, Patrick A., Stamatoyannopoulos, George, Iyer, Vishwanath R., Lieb, Jason D., Sunyaev, Shamil R., Akey, Joshua M., Sabo, Peter J., Kaul, Rajinder, Furey, Terrence S., Dekker, Job, Crawford, Gregory E., and Stamatoyannopoulos, John A.

Subjects
Chromatin -- Physiological aspects, DNA -- Physiological aspects, Genetic research, Human genome -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

DNase I hypersensitive sites (DHSs) are markers of regulatory DNA and have underpinned the discovery of all classes of cis-regulatory elements including enhancers, promoters, insulators, silencers and locus control regions. Here we present the first extensive map of human DHSs identified through genome-wide profiling in 125 diverse cell and tissue types. We identify [similar]2.9 million DHSs that encompass virtually all known experimentally validated cis-regulatory sequences and expose a vast trove of novel elements, most with highly cell-selective regulation. Annotating these elements using ENCODE data reveals novel relationships between chromatin accessibility, transcription, DNA methylation and regulatory factor occupancy patterns. We connect [similar]580,000 distal DHSs with their target promoters, revealing systematic pairing of different classes of distal DHSs and specific promoter types. Patterning of chromatin accessibility at many regulatory regions is organized with dozens to hundreds of co-activated elements, and the transcellular DNase I sensitivity pattern at a given region can predict cell-type-specific functional behaviours. The DHS landscape shows signatures of recent functional evolutionary constraint. However, the DHS compartment in pluripotent and immortalized cells exhibits higher mutation rates than that in highly differentiated cells, exposing an unexpected link between chromatin accessibility, proliferative potential and patterns of human variation., Author(s): Robert E. Thurman [1, 13]; Eric Rynes [1, 13]; Richard Humbert [1, 13]; Jeff Vierstra [1]; Matthew T. Maurano [1]; Eric Haugen [1]; Nathan C. Sheffield [2]; Andrew B. [...]

Published
2012
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45. An expansive human regulatory lexicon encoded in transcription factor footprints

Author

Neph, Shane, Vierstra, Jeff, Stergachis, Andrew B., Reynolds, Alex P., Haugen, Eric, Vernot, Benjamin, Thurman, Robert E., John, Sam, Sandstrom, Richard, Johnson, Audra K., Maurano, Matthew T., Humbert, Richard, Rynes, Eric, Vong, Shinny, Lee, Kristen, Bates, Daniel, Diegel, Morgan, Roach, Vaughn, Dunn, Douglas, Neri, Jun, Schafer, Anthony, Hansen, R. Scott, Kutyavin, Tanya, Giste, Erika, Weaver, Molly, Canfield, Theresa, Sabo, Peter, Zhang, Miaohua, Balasundaram, Gayathri, Byron, Rachel, MacCoss, Michael J., Akey, Joshua M., Bender, M. A., Groudine, Mark, Kaul, Rajinder, and Stamatoyannopoulos, John A.

Subjects
Genetic research, Genetic regulation -- Research, Transcription factors -- Physiological aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Regulatory factor binding to genomic DNA protects the underlying sequence from cleavage by DNase I, leaving nucleotide-resolution footprints. Using genomic DNase I footprinting across 41 diverse cell and tissue types, we detected 45 million transcription factor occupancy events within regulatory regions, representing differential binding to 8.4 million distinct short sequence elements. Here we show that this small genomic sequence compartment, roughly twice the size of the exome, encodes an expansive repertoire of conserved recognition sequences for DNA-binding proteins that nearly doubles the size of the human cis-regulatory lexicon. We find that genetic variants affecting allelic chromatin states are concentrated in footprints, and that these elements are preferentially sheltered from DNA methylation. High-resolution DNase I cleavage patterns mirror nucleotide-level evolutionary conservation and track the crystallographic topography of protein-DNA interfaces, indicating that transcription factor structure has been evolutionarily imprinted on the human genome sequence. We identify a stereotyped 50-base-pair footprint that precisely defines the site of transcript origination within thousands of human promoters. Finally, we describe a large collection of novel regulatory factor recognition motifs that are highly conserved in both sequence and function, and exhibit cell-selective occupancy patterns that closely parallel major regulators of development, differentiation and pluripotency., Author(s): Shane Neph [1, 7]; Jeff Vierstra [1, 7]; Andrew B. Stergachis [1, 7]; Alex P. Reynolds [1, 7]; Eric Haugen [1]; Benjamin Vernot [1]; Robert E. Thurman [1]; Sam [...]

Published
2012
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48. MOUSE GENOMICS: Mouse regulatory DNA landscapes reveal global principles of cis-regulatory evolution

Author

Vierstra, Jeff, Rynes, Eric, Sandstrom, Richard, Zhang, Miaohua, Canfield, Theresa, Hansen, Scott R., Stehling-Sun, Sandra, Sabo, Peter J., Byron, Rachel, Humbert, Richard, Thurman, Robert E., Johnson, Audra K., Vong, Shinny, Lee, Kristen, Bates, Daniel, Neri, Fidencio, Diegel, Morgan, Giste, Erika, Haugen, Eric, Dunn, Douglas, Wilken, Matthew S., Josefowicz, Steven, Samstein, Robert, Chang, Kai-Hsin, Eichler, Evan E., De Bruijn, Marella, Reh, Thomas A., Skoultchi, Arthur, Rudensky, Alexander, Orkin, Stuart H., Papayannopoulou, Thalia, Treuting, Piper M., Selleri, Licia, Kaul, Rajinder, Groudine, Mark, Bender, M. A., and Stamatoyannopoulos, John A.

Published
2014
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49. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project

Author

Birney, Ewan, Stamatoyannopoulos, John A., Dutta, Anindya, Guigo, Roderic, Gingeras, Thomas R., Margulies, Elliott H., Weng, Zhiping, Snyder, Michael, Dermitzakis, Emmanouil T., Thurman, Robert E., Kuehn, Michael S., Taylor, Christopher M., Neph, Shane, Koch, Christoph M., Asthana, Saurabh, Malhotra, Ankit, Adzhubei, Ivan, Greenbaum, Jason A., Andrews, Robert M., Flicek, Paul, Boyle, Patrick J., Cao, Hua, Carter, Nigel P., Clelland, Gayle K., Davis, Sean, Day, Nathan, Dhami, Pawandeep, Dillon, Shane C., Dorschner, Michael O., Fiegler, Heike, Giresi, Paul G., Goldy, Jeff, Hawrylycz, Michael, Haydock, Andrew, Humbert, Richard, James, Keith D., Johnson, Brett E., Johnson, Ericka M., Frum, Tristan T., Rosenzweig, Elizabeth R., Karnani, Neerja, Lee, Kirsten, Lefebvre, Gregory C., Navas, Patrick A., Neri, Fidencio, Parker, Stephen C. J., Sabo, Peter J., Sandstrom, Richard, Shafer, Anthony, Vetrie, David, Weaver, Molly, Wilcox, Sarah, Yu1, Man, Collins, Francis S., Dekker, Job, Lieb, Jason D., Tullius, Thomas D., Crawford, Gregory E., Sunyaev, Shamil, Noble, William S., Dunham, Ian, Denoeud, France, Reymond, Alexandre, Kapranov, Philipp, Rozowsky, Joel, Zheng, Deyou, Castelo, Robert, Frankish, Adam, Harrow, Jennifer, Ghosh, Srinka, Sandelin, Albin, Hofacker, Ivo L., Baertsch, Robert, Keefe, Damian, Dike, Sujit, Cheng, Jill, Hirsch, Heather A., Sekinger, Edward A., Lagarde, Julien, Abril, Josep F., Shahab, Atif, Flamm, Christoph, Fried, Claudia, Hackermuller, Jorg, Hertel, Jana, Lindemeyer, Manja, Missal, Kristin, Tanzer, Andrea, Washietl, Stefan, Korbel, Jan, Emanuelsson, Olof, Pedersen, Jakob S., Holroyd, Nancy, Taylor, Ruth, Swarbreck, David, Matthews, Nicholas, Dickson, Mark C., Thomas, Daryl J., Weirauch, Matthew T., Gilbert, James, Drenkow, Jorg, Bell, Ian, Zhao, XiaoDong, Srinivasan, K.G., Sung, Wing-Kin, Ooi, Hong Sain, Chiu, Kuo Ping, Foissac, Sylvain, Alioto, Tyler, Brent, Michael, Pachter, Lior, Tress, Michael L., Valencia, Alfonso, Choo, Siew Woh, Choo, Chiou Yu, Ucla, Catherine, Manzano, Caroline, Wyss, Carine, Cheung, Evelyn, Clark, Taane G., Brown, James B., Ganesh, Madhavan, Patel, Sandeep, Tammana, Hari, Chrast, Jacqueline, Henrichsen, Charlotte N., Kai, Chikatoshi, Kawai, Jun, Nagalakshmi, Ugrappa, Wu, Jiaqian, Lian, Zheng, Lian, Jin, Newburger, Peter, Zhang, Xueqing, Bickel, Peter, Mattick, John S., Carninci, Piero, Hayashizaki, Yoshihide, Weissman, Sherman, Hubbard, Tim, Myers, Richard M., Rogers, Jane, Stadler, Peter F., Lowe, Todd M., Wei, Chia-Lin, Ruan, Yijun, Struhl, Kevin, Gerstein, Mark, Antonarakis, Stylianos E., Fu, Yutao, Green, Eric D., Karaoz, Ulaş, Siepel, Adam, Taylor, James, Liefer, Laura A., Wetterstrand, Kris A., Good, Peter J., Feingold, Elise A., Guyer, Mark S., Cooper, Gregory M., Asimenos, George, Dewey, Colin N., Hou, Minmei, Nikolaev, Sergey, Montoya-Burgos, Juan I., Loytynoja, Ari, Whelan, Simon, Pardi, Fabio, Massingham, Tim, Huang, Haiyan, Zhang, Nancy R., Holmes, Ian, Mullikin, James C., Ureta-Vidal, Abel, Paten, Benedict, Seringhaus, Michael, Church, Deanna, Rosenbloom, Kate, Kent, W. 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Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): The ENCODE Project Consortium; Analysis Coordination; Ewan Birney (corresponding author) [1]; John A. Stamatoyannopoulos (corresponding author) [2]; Anindya Dutta (corresponding author) [3]; Roderic Guigó (corresponding author) [4, 5]; Thomas [...]

Published
2007
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