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32 results on '"Eaton, Matthew L"'

1. Novel epigenomic liquid biopsy assay to predict estrogen receptor (ER) status and to infer ER pathway activation in breast cancer.

Author

Morganti, Stefania, primary, Beagan, Jonathan, additional, D'Ippolito, Anthony, additional, Smith, Kalie, additional, Hughes, Melissa E., additional, Chmielecki, Juliann, additional, Gorthi, Aparna, additional, Painter, Corrie, additional, Barrett, J. Carl, additional, Eaton, Matthew L, additional, Freedman, Matthew, additional, Tolaney, Sara M., additional, Lin, Nancy U., additional, and Parsons, Heather Anne, additional

Published
2024
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2. Alzheimer's disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci

Author

De Jager, Philip L, Srivastava, Gyan, Lunnon, Katie, Burgess, Jeremy, Schalkwyk, Leonard C, Yu, Lei, Eaton, Matthew L, Keenan, Brendan T, Ernst, Jason, McCabe, Cristin, Tang, Anna, Raj, Towfique, Replogle, Joseph, Brodeur, Wendy, Gabriel, Stacey, Chai, High S, Younkin, Curtis, Younkin, Steven G, Zou, Fanggeng, Szyf, Moshe, Epstein, Charles B, Schneider, Julie A, Bernstein, Bradley E, Meissner, Alex, Ertekin-Taner, Nilufer, Chibnik, Lori B, Kellis, Manolis, Mill, Jonathan, and Bennett, David A

Subjects
Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain Disorders, Alzheimer's Disease, Human Genome, Genetics, Dementia, Neurodegenerative, Acquired Cognitive Impairment, Aging, 2.1 Biological and endogenous factors, Aetiology, Neurological, Adaptor Proteins, Signal Transducing, Aged, Aged, 80 and over, Alzheimer Disease, Amyloidosis, Ankyrins, Brain, Carrier Proteins, CpG Islands, DNA Methylation, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Intracellular Signaling Peptides and Proteins, Male, Middle Aged, Nuclear Proteins, Protein Interaction Maps, Tumor Suppressor Proteins, Psychology, Cognitive Sciences, Neurology & Neurosurgery
Abstract

We used a collection of 708 prospectively collected autopsied brains to assess the methylation state of the brain's DNA in relation to Alzheimer's disease (AD). We found that the level of methylation at 71 of the 415,848 interrogated CpGs was significantly associated with the burden of AD pathology, including CpGs in the ABCA7 and BIN1 regions, which harbor known AD susceptibility variants. We validated 11 of the differentially methylated regions in an independent set of 117 subjects. Furthermore, we functionally validated these CpG associations and identified the nearby genes whose RNA expression was altered in AD: ANK1, CDH23, DIP2A, RHBDF2, RPL13, SERPINF1 and SERPINF2. Our analyses suggest that these DNA methylation changes may have a role in the onset of AD given that we observed them in presymptomatic subjects and that six of the validated genes connect to a known AD susceptibility gene network.

Published
2014

3. Supplementary Table S3: Median Survival By Cluster from Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist

Author

McKeown, Michael R., primary, Corces, M. Ryan, primary, Eaton, Matthew L., primary, Fiore, Chris, primary, Lee, Emily, primary, Lopez, Jeremy T., primary, Chen, Mei Wei, primary, Smith, Darren, primary, Chan, Steven M., primary, Koenig, Julie L., primary, Austgen, Kathryn, primary, Guenther, Matthew G., primary, Orlando, David A., primary, Lovén, Jakob, primary, Fritz, Christian C., primary, and Majeti, Ravindra, primary

Published
2023
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4. Supplementary Table S2: mRNA Cluster Signatures from Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist

Author

McKeown, Michael R., primary, Corces, M. Ryan, primary, Eaton, Matthew L., primary, Fiore, Chris, primary, Lee, Emily, primary, Lopez, Jeremy T., primary, Chen, Mei Wei, primary, Smith, Darren, primary, Chan, Steven M., primary, Koenig, Julie L., primary, Austgen, Kathryn, primary, Guenther, Matthew G., primary, Orlando, David A., primary, Lovén, Jakob, primary, Fritz, Christian C., primary, and Majeti, Ravindra, primary

Published
2023
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5. Supplementary Table S1: Sample mutations from Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist

Author

McKeown, Michael R., primary, Corces, M. Ryan, primary, Eaton, Matthew L., primary, Fiore, Chris, primary, Lee, Emily, primary, Lopez, Jeremy T., primary, Chen, Mei Wei, primary, Smith, Darren, primary, Chan, Steven M., primary, Koenig, Julie L., primary, Austgen, Kathryn, primary, Guenther, Matthew G., primary, Orlando, David A., primary, Lovén, Jakob, primary, Fritz, Christian C., primary, and Majeti, Ravindra, primary

Published
2023
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6. Supplementary Table S4: Enhancer, mRNA, and SY-1425 EC50 in AML cell lines from Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist

Author

McKeown, Michael R., primary, Corces, M. Ryan, primary, Eaton, Matthew L., primary, Fiore, Chris, primary, Lee, Emily, primary, Lopez, Jeremy T., primary, Chen, Mei Wei, primary, Smith, Darren, primary, Chan, Steven M., primary, Koenig, Julie L., primary, Austgen, Kathryn, primary, Guenther, Matthew G., primary, Orlando, David A., primary, Lovén, Jakob, primary, Fritz, Christian C., primary, and Majeti, Ravindra, primary

Published
2023
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7. Supplementary Methods and Figure Legends from Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist

Author

McKeown, Michael R., primary, Corces, M. Ryan, primary, Eaton, Matthew L., primary, Fiore, Chris, primary, Lee, Emily, primary, Lopez, Jeremy T., primary, Chen, Mei Wei, primary, Smith, Darren, primary, Chan, Steven M., primary, Koenig, Julie L., primary, Austgen, Kathryn, primary, Guenther, Matthew G., primary, Orlando, David A., primary, Lovén, Jakob, primary, Fritz, Christian C., primary, and Majeti, Ravindra, primary

Published
2023
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8. Supplementary Table S7: GREAT analysis from Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist

Author

McKeown, Michael R., primary, Corces, M. Ryan, primary, Eaton, Matthew L., primary, Fiore, Chris, primary, Lee, Emily, primary, Lopez, Jeremy T., primary, Chen, Mei Wei, primary, Smith, Darren, primary, Chan, Steven M., primary, Koenig, Julie L., primary, Austgen, Kathryn, primary, Guenther, Matthew G., primary, Orlando, David A., primary, Lovén, Jakob, primary, Fritz, Christian C., primary, and Majeti, Ravindra, primary

Published
2023
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9. Data from Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist

Author

McKeown, Michael R., primary, Corces, M. Ryan, primary, Eaton, Matthew L., primary, Fiore, Chris, primary, Lee, Emily, primary, Lopez, Jeremy T., primary, Chen, Mei Wei, primary, Smith, Darren, primary, Chan, Steven M., primary, Koenig, Julie L., primary, Austgen, Kathryn, primary, Guenther, Matthew G., primary, Orlando, David A., primary, Lovén, Jakob, primary, Fritz, Christian C., primary, and Majeti, Ravindra, primary

Published
2023
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10. Supplementary Figures from Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist

Author

McKeown, Michael R., primary, Corces, M. Ryan, primary, Eaton, Matthew L., primary, Fiore, Chris, primary, Lee, Emily, primary, Lopez, Jeremy T., primary, Chen, Mei Wei, primary, Smith, Darren, primary, Chan, Steven M., primary, Koenig, Julie L., primary, Austgen, Kathryn, primary, Guenther, Matthew G., primary, Orlando, David A., primary, Lovén, Jakob, primary, Fritz, Christian C., primary, and Majeti, Ravindra, primary

Published
2023
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11. Supplementary Table S5 & 6: GSEA of SY-1425 response from Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist

Author

McKeown, Michael R., primary, Corces, M. Ryan, primary, Eaton, Matthew L., primary, Fiore, Chris, primary, Lee, Emily, primary, Lopez, Jeremy T., primary, Chen, Mei Wei, primary, Smith, Darren, primary, Chan, Steven M., primary, Koenig, Julie L., primary, Austgen, Kathryn, primary, Guenther, Matthew G., primary, Orlando, David A., primary, Lovén, Jakob, primary, Fritz, Christian C., primary, and Majeti, Ravindra, primary

Published
2023
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15. 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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16. Abstract PR05: SY-1425 (tamibarotene), a potent and selective RARα agonist, induces changes in the transcriptional regulatory circuit of AML cells leading to differentiation

Author

Fiore, Christopher M., primary, McKeown, Michael R., additional, Lee, Emily, additional, Eaton, Matthew L., additional, Smith, Darren, additional, Austgen, Kathryn, additional, Chen, Mei Wei, additional, Guenther, Matthew, additional, Corces, M. Ryan, additional, Majeti, Ravindra, additional, Olson, Eric, additional, and Fritz, Christian C., additional

Published
2017
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17. Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist

Author

McKeown, Michael R., primary, Corces, M. Ryan, additional, Eaton, Matthew L., additional, Fiore, Chris, additional, Lee, Emily, additional, Lopez, Jeremy T., additional, Chen, Mei Wei, additional, Smith, Darren, additional, Chan, Steven M., additional, Koenig, Julie L., additional, Austgen, Kathryn, additional, Guenther, Matthew G., additional, Orlando, David A., additional, Lovén, Jakob, additional, Fritz, Christian C., additional, and Majeti, Ravindra, additional

Published
2017
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23. BRCA1 Recruitment to Transcriptional Pause Sites Is Required for R-Loop-Driven DNA Damage Repair

Author

Hatchi, Elodie, Skourti-Stathaki, Konstantina, Ventz, Steffen, Pinello, Luca, Yen, Angela, Kamieniarz-Gdula, Kinga, Dimitrov, Stoil, Pathania, Shailja, McKinney, Kristine M., Eaton, Matthew L., Kellis, Manolis, Hill, Sarah J., Parmigiani, Giovanni, Proudfoot, Nicholas J., Livingston, David M., Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Yen, Angela, Eaton, Matthew Lucas, and Kellis, Manolis

Subjects
Cell Biology, Molecular Biology
Abstract

The mechanisms contributing to transcription-associated genomic instability are both complex and incompletely understood. Although R-loops are normal transcriptional intermediates, they are also associated with genomic instability. Here, we show that BRCA1 is recruited to R-loops that form normally over a subset of transcription termination regions. There it mediates the recruitment of a specific, physiological binding partner, senataxin (SETX). Disruption of this complex led to R-loop-driven DNA damage at those loci as reflected by adjacent γ-H2AX accumulation and ssDNA breaks within the untranscribed strand of relevant R-loop structures. Genome-wide analysis revealed widespread BRCA1 binding enrichment at R-loop-rich termination regions (TRs) of actively transcribed genes. Strikingly, within some of these genes in BRCA1 null breast tumors, there are specific insertion/deletion mutations located close to R-loop-mediated BRCA1 binding sites within TRs. Thus, BRCA1/SETX complexes support a DNA repair mechanism that addresses R-loop-based DNA damage at transcriptional pause sites.

Published
2014

24. Alzheimer's disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci

Author

Srivastava, Gyan, Lunnon, Katie, Burgess, Jeremy, Yu, Lei, Ernst, Jason, McCabe, Cristin, Tang, Anna, Raj, Towfique, Replogle, Joseph, Brodeur, Wendy, Gabriel, Stacey, Younkin, Curtis, Zou, Fanggeng, Szyf, Moshe, Meissner, Alexander, Ertekin-Taner, Nilufer, Kellis, Manolis, Mill, Jonathan, De Jager, Philip L., Schalkwyk, Leonard C., Eaton, Matthew Lucas, Eaton, Matthew L., Keenan, Brendan T., Chai, High S., Younkin, Steven G., Epstein, Charles B., Schneider, Julie A., Bernstein, Bradley E., Chibnik, Lori B., Bennett, David A., Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Eaton, Matthew Lucas, Ernst, Jason, Meissner, Alexander, and Kellis, Manolis

Subjects
Male, Aging, Genome-wide association study, Neurodegenerative, Alzheimer's Disease, 80 and over, 2.1 Biological and endogenous factors, Psychology, Protein Interaction Maps, Aetiology, Epigenomics, Genetics, Aged, 80 and over, General Neuroscience, Intracellular Signaling Peptides and Proteins, Brain, Adaptor Proteins, Nuclear Proteins, Methylation, Amyloidosis, Middle Aged, 3. Good health, CpG site, Neurological, DNA methylation, Female, Cognitive Sciences, Alzheimer's disease, Ankyrins, and over, Biology, Article, Alzheimer Disease, Acquired Cognitive Impairment, medicine, Humans, Genetic Predisposition to Disease, Gene, Adaptor Proteins, Signal Transducing, Aged, Neurology & Neurosurgery, Tumor Suppressor Proteins, Human Genome, Signal Transducing, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), DNA Methylation, medicine.disease, Brain Disorders, Differentially methylated regions, Dementia, CpG Islands, Carrier Proteins, Genome-Wide Association Study
Abstract

We used a collection of 708 prospectively collected autopsied brains to assess the methylation state of the brain's DNA in relation to Alzheimer's disease (AD). We found that the level of methylation at 71 of the 415,848 interrogated CpGs was significantly associated with the burden of AD pathology, including CpGs in the ABCA7 and BIN1 regions, which harbor known AD susceptibility variants. We validated 11 of the differentially methylated regions in an independent set of 117 subjects. Furthermore, we functionally validated these CpG associations and identified the nearby genes whose RNA expression was altered in AD: ANK1, CDH23, DIP2A, RHBDF2, RPL13, SERPINF1 and SERPINF2. Our analyses suggest that these DNA methylation changes may have a role in the onset of AD given that we observed them in presymptomatic subjects and that six of the validated genes connect to a known AD susceptibility gene network., National Institutes of Health (U.S.) (Grant R01 AG036042), National Institutes of Health (U.S.) (Grant R01AG036836), National Institutes of Health (U.S.) (Grant R01 AG17917), National Institutes of Health (U.S.) (Grant R01AG15819), National Institutes of Health (U.S.) (Grant R01 AG032990), National Institutes of Health (U.S.) (Grant R01 AG18023), National Institutes of Health (U.S.) (Grant RC2 AG036547), National Institutes of Health (U.S.) (Grant P30 AG10161), National Institutes of Health (U.S.) (Grant P50 AG016574), National Institutes of Health (U.S.) (Grant U01 ES017155), National Institutes of Health (U.S.) (Grant KL2 RR024151), National Institutes of Health (U.S.) (Grant K25 AG041906-01)

Published
2014

29. BRCA1 Recruitment to Transcriptional Pause Sites Is Required for R-Loop-Driven DNA Damage Repair

Author

Hatchi, Elodie, primary, Skourti-Stathaki, Konstantina, additional, Ventz, Steffen, additional, Pinello, Luca, additional, Yen, Angela, additional, Kamieniarz-Gdula, Kinga, additional, Dimitrov, Stoil, additional, Pathania, Shailja, additional, McKinney, Kristine M., additional, Eaton, Matthew L., additional, Kellis, Manolis, additional, Hill, Sarah J., additional, Parmigiani, Giovanni, additional, Proudfoot, Nicholas J., additional, and Livingston, David M., additional

Published
2015
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30. Noncoding Transcription Is a Driving Force for Nucleosome Instability in spt16 Mutant Cells.

Author

Jianxun Feng, Haiyun Gan, Eaton, Matthew L., Hui Zhou, Shuqi Li, Belsky, Jason A., MacAlpine, David M., Zhiguo Zhang, and Qing Li

Subjects
CHROMATIN, HISTONES, GENETIC mutation, RNA polymerase II, GENETIC transcription
Abstract

FACT (facilitates chromatin transcription) consists of two essential subunits, Spt16 and Pob3, and functions as a histone chaperone. Mutation of spt16 results in a global loss of nucleosomes as well as aberrant transcription. Here, we show that the majority of nucleosome changes upon Spt16 depletion are alterations in nucleosome fuzziness and position shift. Most nucleosomal changes are suppressed by the inhibition of RNA polymerase II (Pol II) activity. Surprisingly, a small subgroup of nucleosome changes is resistant to transcriptional inhibition. Notably, Spt16 and distinct histone modifications are enriched at this subgroup of nucleosomes. We also report 1,037 Spt16-suppressed noncoding transcripts (SNTs) and found that the SNT start sites are enriched with the subgroup of nucleosomes resistant to Pol II inhibition. Finally, the nucleosomes at genes overlapping SNTs are more susceptible to changes upon Spt16 depletion than those without SNTs. Taken together, our results support a model in which Spt16 has a role in maintaining local nucleosome stability to inhibit initiation of SNT transcription, which once initiated drives additional nucleosome loss upon Spt16 depletion. [ABSTRACT FROM AUTHOR]

Published
2016
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31. Integrative analysis of 111 reference human epigenomes.

Author

Roadmap Epigenomics Consortium, Kundaje, Anshul, Meuleman, Wouter, Ernst, Jason, Bilenky, Misha, Yen, Angela, Heravi-Moussavi, Alireza, Kheradpour, Pouya, Zhang, Zhizhuo, Wang, Jianrong, Ziller, Michael J., Amin, Viren, Whitaker, John W., Schultz, Matthew D., Ward, Lucas D., Sarkar, Abhishek, Quon, Gerald, Sandstrom, Richard S., Eaton, Matthew L., and Wu, Yi-Chieh

Subjects
EPIGENETICS, HUMAN genetic variation, GENOMICS, CELL differentiation
Abstract

The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease. [ABSTRACT FROM AUTHOR]

Published
2015
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32. Integrative analysis of 111 reference human epigenomes

Author

Kundaje, Anshul, Meuleman, Wouter, Ernst, Jason, Bilenky, Misha, Yen, Angela, Kheradpour, Pouya, Zhang, Zhizhuo, Heravi-Moussavi, Alireza, Liu, Yaping, Amin, Viren, Ziller, Michael J, Whitaker, John W, Schultz, Matthew D, Sandstrom, Richard S, Eaton, Matthew L, Wu, Yi-Chieh, Wang, Jianrong, Ward, Lucas D, Sarkar, Abhishek, Quon, Gerald, Pfenning, Andreas, Wang, Xinchen, Claussnitzer, Melina, Coarfa, Cristian, Harris, R Alan, Shoresh, Noam, Epstein, Charles B, Gjoneska, Elizabeta, Leung, Danny, Xie, Wei, Hawkins, R David, Lister, Ryan, Hong, Chibo, Gascard, Philippe, Mungall, Andrew J, Moore, Richard, Chuah, Eric, Tam, Angela, Canfield, Theresa K, Hansen, R Scott, Kaul, Rajinder, Sabo, Peter J, Bansal, Mukul S, Carles, Annaick, Dixon, Jesse R, Farh, Kai-How, Feizi, Soheil, Karlic, Rosa, Kim, Ah-Ram, Kulkarni, Ashwinikumar, Li, Daofeng, Lowdon, Rebecca, Mercer, Tim R, Neph, Shane J, Onuchic, Vitor, Polak, Paz, Rajagopal, Nisha, Ray, Pradipta, Sallari, Richard C, Siebenthall, Kyle T, Sinnott-Armstrong, Nicholas, Stevens, Michael, Thurman, Robert E, Wu, Jie, Zhang, Bo, Zhou, Xin, Beaudet, Arthur E, Boyer, Laurie A, De Jager, Philip, Farnham, Peggy J, Fisher, Susan J, Haussler, David, Jones, Steven, Li, Wei, Marra, Marco, McManus, Michael T, Sunyaev, Shamil, Thomson, James A, Tlsty, Thea D, Tsai, Li-Huei, Wang, Wei, Waterland, Robert A, Zhang, Michael, Chadwick, Lisa H, Bernstein, Bradley E, Costello, Joseph F, Ecker, Joseph R, Hirst, Martin, Meissner, Alexander, Milosavljevic, Aleksandar, Ren, Bing, Stamatoyannopoulos, John A, Wang, Ting, and Kellis, Manolis

Abstract

The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but a similar reference has lacked for epigenomic studies. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection to-date of human epigenomes for primary cells and tissues. Here, we describe the integrative analysis of 111 reference human epigenomes generated as part of the program, profiled for histone modification patterns, DNA accessibility, DNA methylation, and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically-relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation, and human disease.

Published
2015
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