Search

Your search keyword '"Klein, Isaac A."' showing total 16 results
Start Over Author "Klein, Isaac A." Publisher elsevier bv
16 results on '"Klein, Isaac A."'

2. Biomolecular Condensates and Cancer

Author

Massachusetts Institute of Technology. Department of Biology, Boija, Ann, Klein, Isaac A., Young, Richard A., Massachusetts Institute of Technology. Department of Biology, Boija, Ann, Klein, Isaac A., and Young, Richard A.

Abstract

Malignant transformation is characterized by dysregulation of diverse cellular processes that have been the subject of detailed genetic, biochemical, and structural studies, but only recently has evidence emerged that many of these processes occur in the context of biomolecular condensates. Condensates are membrane-less bodies, often formed by liquid-liquid phase separation, that compartmentalize protein and RNA molecules with related functions. New insights from condensate studies portend a profound transformation in our understanding of cellular dysregulation in cancer. Here we summarize key features of biomolecular condensates, note where they have been implicated—or will likely be implicated—in oncogenesis, describe evidence that the pharmacodynamics of cancer therapeutics can be greatly influenced by condensates, and discuss some of the questions that must be addressed to further advance our understanding and treatment of cancer., NIH (Grants GM123511, CA213333 and CA155258)

Published
2021

3. Enhancer Features that Drive Formation of Transcriptional Condensates

Author

Massachusetts Institute of Technology. Department of Chemical Engineering, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology. Department of Physics, Ragon Institute of MGH, MIT and Harvard, Massachusetts Institute of Technology. Department of Chemistry, Shrinivas, Krishna, Sabari, Benjamin R, Coffey, Eliot L, Klein, Isaac A, Boija, Ann, Zamudio, Alicia V, Schuijers, Jurian, Hannett, Nancy M, Sharp, Phillip A, Young, Richard A, Chakraborty, Arup K, Massachusetts Institute of Technology. Department of Chemical Engineering, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology. Department of Physics, Ragon Institute of MGH, MIT and Harvard, Massachusetts Institute of Technology. Department of Chemistry, Shrinivas, Krishna, Sabari, Benjamin R, Coffey, Eliot L, Klein, Isaac A, Boija, Ann, Zamudio, Alicia V, Schuijers, Jurian, Hannett, Nancy M, Sharp, Phillip A, Young, Richard A, and Chakraborty, Arup K

Abstract

© 2019 Elsevier Inc. Enhancers are DNA elements that are bound by transcription factors (TFs), which recruit coactivators and the transcriptional machinery to genes. Phase-separated condensates of TFs and coactivators have been implicated in assembling the transcription machinery at particular enhancers, yet the role of DNA sequence in this process has not been explored. We show that DNA sequences encoding TF binding site number, density, and affinity above sharply defined thresholds drive condensation of TFs and coactivators. A combination of specific structured (TF-DNA) and weak multivalent (TF-coactivator) interactions allows for condensates to form at particular genomic loci determined by the DNA sequence and the complement of expressed TFs. DNA features found to drive condensation promote enhancer activity and transcription in cells. Our study provides a framework to understand how the genome can scaffold transcriptional condensates at specific loci and how the universal phenomenon of phase separation might regulate this process. Shrinivas et al. demonstrate that specific types of motif compositions encoded in DNA drive localized formation of transcriptional condensates. These findings explain how phase separation can occur at specific genomic locations and shed light on why only some genomic loci become highly active enhancers.

Published
2021

4. Transcription Factors Activate Genes through the Phase-Separation Capacity of Their Activation Domains

Author

Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Chemical Engineering, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Klein, Isaac A., Sabari, Benjamin R., Dall’Agnese, Alessandra, Coffey, Eliot L., Zamudio, Alicia V., Manteiga, John C., Hannett, Nancy M., Abraham, Brian J., Afeyan, Lena K., Guo, Yang E., Schuijers, Jurian, Lee, Tong Ihn, Taatjes, Dylan J., Young, Richard A., Shrinivas, Krishna,Ph. D.Massachusetts Institute of Technology., Li, Charles H., Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Chemical Engineering, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Klein, Isaac A., Sabari, Benjamin R., Dall’Agnese, Alessandra, Coffey, Eliot L., Zamudio, Alicia V., Manteiga, John C., Hannett, Nancy M., Abraham, Brian J., Afeyan, Lena K., Guo, Yang E., Schuijers, Jurian, Lee, Tong Ihn, Taatjes, Dylan J., Young, Richard A., Shrinivas, Krishna,Ph. D.Massachusetts Institute of Technology., and Li, Charles H.

Abstract

Gene expression is controlled by transcription factors (TFs) that consist of DNA-binding domains (DBDs) and activation domains (ADs). The DBDs have been well characterized, but little is known about the mechanisms by which ADs effect gene activation. Here, we report that diverse ADs form phase-separated condensates with the Mediator coactivator. For the OCT4 and GCN4 TFs, we show that the ability to form phase-separated droplets with Mediator in vitro and the ability to activate genes in vivo are dependent on the same amino acid residues. For the estrogen receptor (ER), a ligand-dependent activator, we show that estrogen enhances phase separation with Mediator, again linking phase separation with gene activation. These results suggest that diverse TFs can interact with Mediator through the phase-separating capacity of their ADs and that formation of condensates with Mediator is involved in gene activation., National Institutes of Health (U.S.) (Grant GM123511), National Institutes of Health (U.S.) (Grant GM117370), Swedish Research Council (Postdoctoral Fellowship VR 2017-00372), Damon Runyon Cancer Research Foundation ( Fellowship 2309-17)

Published
2020

6. Mediator Condensates Localize Signaling Factors to Key Cell Identity Genes

Author

Zamudio, Alicia V., primary, Dall’Agnese, Alessandra, additional, Henninger, Jonathan E., additional, Manteiga, John C., additional, Afeyan, Lena K., additional, Hannett, Nancy M., additional, Coffey, Eliot L., additional, Li, Charles H., additional, Oksuz, Ozgur, additional, Sabari, Benjamin R., additional, Boija, Ann, additional, Klein, Isaac A., additional, Hawken, Susana W., additional, Spille, Jan-Hendrik, additional, Decker, Tim-Michael, additional, Cisse, Ibrahim I., additional, Abraham, Brian J., additional, Lee, Tong I., additional, Taatjes, Dylan J., additional, Schuijers, Jurian, additional, and Young, Richard A., additional

Published
2019
Full Text
View/download PDF

7. Enhancer Features that Drive Formation of Transcriptional Condensates

Author

Shrinivas, Krishna, primary, Sabari, Benjamin R., additional, Coffey, Eliot L., additional, Klein, Isaac A., additional, Boija, Ann, additional, Zamudio, Alicia V., additional, Schuijers, Jurian, additional, Hannett, Nancy M., additional, Sharp, Phillip A., additional, Young, Richard A., additional, and Chakraborty, Arup K., additional

Published
2019
Full Text
View/download PDF

8. Transcription Factors Activate Genes through the Phase-Separation Capacity of Their Activation Domains

Author

Boija, Ann, primary, Klein, Isaac A., additional, Sabari, Benjamin R., additional, Dall’Agnese, Alessandra, additional, Coffey, Eliot L., additional, Zamudio, Alicia V., additional, Li, Charles H., additional, Shrinivas, Krishna, additional, Manteiga, John C., additional, Hannett, Nancy M., additional, Abraham, Brian J., additional, Afeyan, Lena K., additional, Guo, Yang E., additional, Rimel, Jenna K., additional, Fant, Charli B., additional, Schuijers, Jurian, additional, Lee, Tong Ihn, additional, Taatjes, Dylan J., additional, and Young, Richard A., additional

Published
2018
Full Text
View/download PDF

11. Translocation-Capture Sequencing Reveals the Extent and Nature of Chromosomal Rearrangements in B Lymphocytes

Author

Klein, Isaac A., primary, Resch, Wolfgang, additional, Jankovic, Mila, additional, Oliveira, Thiago, additional, Yamane, Arito, additional, Nakahashi, Hirotaka, additional, Di Virgilio, Michela, additional, Bothmer, Anne, additional, Nussenzweig, Andre, additional, Robbiani, Davide F., additional, Casellas, Rafael, additional, and Nussenzweig, Michel C., additional

Published
2011
Full Text
View/download PDF

12. Regulation of DNA End Joining, Resection, and Immunoglobulin Class Switch Recombination by 53BP1

Author

Bothmer, Anne, primary, Robbiani, Davide F., additional, Di Virgilio, Michela, additional, Bunting, Samuel F., additional, Klein, Isaac A., additional, Feldhahn, Niklas, additional, Barlow, Jacqueline, additional, Chen, Hua-Tang, additional, Bosque, David, additional, Callen, Elsa, additional, Nussenzweig, André, additional, and Nussenzweig, Michel C., additional

Published
2011
Full Text
View/download PDF

13. Activation-Induced Cytidine Deaminase Targets DNA at Sites of RNA Polymerase II Stalling by Interaction with Spt5

Author

Pavri, Rushad, primary, Gazumyan, Anna, additional, Jankovic, Mila, additional, Di Virgilio, Michela, additional, Klein, Isaac, additional, Ansarah-Sobrinho, Camilo, additional, Resch, Wolfgang, additional, Yamane, Arito, additional, San-Martin, Bernardo Reina, additional, Barreto, Vasco, additional, Nieland, Thomas J., additional, Root, David E., additional, Casellas, Rafael, additional, and Nussenzweig, Michel C., additional

Published
2010
Full Text
View/download PDF

14. AID Produces DNA Double-Strand Breaks in Non-Ig Genes and Mature B Cell Lymphomas with Reciprocal Chromosome Translocations

Author

Robbiani, Davide F., primary, Bunting, Samuel, additional, Feldhahn, Niklas, additional, Bothmer, Anne, additional, Camps, Jordi, additional, Deroubaix, Stephanie, additional, McBride, Kevin M., additional, Klein, Isaac A., additional, Stone, Gary, additional, Eisenreich, Thomas R., additional, Ried, Thomas, additional, Nussenzweig, André, additional, and Nussenzweig, Michel C., additional

Published
2009
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results