Combinatorial Patterning of Chromatin Regulators Uncovered by Genome-wide Location Analysis in Human Cells
Hundreds of chromatin regulators (CRs) control chromatin structure and function by catalyzing and binding histone modifications, yet the rules governing these key processes remain obscure. Here, we present a systematic approach to infer CR function. We developed ChIP-string, a meso-scale assay that...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2014
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| Online Access: | http://hdl.handle.net/1721.1/92255 https://orcid.org/0000-0001-8567-2049 https://orcid.org/0000-0002-6086-3903 |
| _version_ | 1826198436551065600 |
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| author | Ram, Oren Goren, Alon Amit, Ido Shoresh, Noam Yosef, Nir Ernst, Jason Kellis, Manolis Issner, Robbyn Durham, Timothy Zhang, Xiaolan Donaghey, Julie Epstein, Charles B. Regev, Aviv Bernstein, Bradley E. Gymrek, Melissa A. Coyne, Michael J. |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Ram, Oren Goren, Alon Amit, Ido Shoresh, Noam Yosef, Nir Ernst, Jason Kellis, Manolis Issner, Robbyn Durham, Timothy Zhang, Xiaolan Donaghey, Julie Epstein, Charles B. Regev, Aviv Bernstein, Bradley E. Gymrek, Melissa A. Coyne, Michael J. |
| author_sort | Ram, Oren |
| collection | MIT |
| description | Hundreds of chromatin regulators (CRs) control chromatin structure and function by catalyzing and binding histone modifications, yet the rules governing these key processes remain obscure. Here, we present a systematic approach to infer CR function. We developed ChIP-string, a meso-scale assay that combines chromatin immunoprecipitation with a signature readout of 487 representative loci. We applied ChIP-string to screen 145 antibodies, thereby identifying effective reagents, which we used to map the genome-wide binding of 29 CRs in two cell types. We found that specific combinations of CRs colocalize in characteristic patterns at distinct chromatin environments, at genes of coherent functions, and at distal regulatory elements. When comparing between cell types, CRs redistribute to different loci but maintain their modular and combinatorial associations. Our work provides a multiplex method that substantially enhances the ability to monitor CR binding, presents a large resource of CR maps, and reveals common principles for combinatorial CR function. |
| first_indexed | 2024-09-23T11:04:55Z |
| format | Article |
| id | mit-1721.1/92255 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:04:55Z |
| publishDate | 2014 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/922552022-10-01T01:01:28Z Combinatorial Patterning of Chromatin Regulators Uncovered by Genome-wide Location Analysis in Human Cells Ram, Oren Goren, Alon Amit, Ido Shoresh, Noam Yosef, Nir Ernst, Jason Kellis, Manolis Issner, Robbyn Durham, Timothy Zhang, Xiaolan Donaghey, Julie Epstein, Charles B. Regev, Aviv Bernstein, Bradley E. Gymrek, Melissa A. Coyne, Michael J. Harvard University--MIT Division of Health Sciences and Technology Lincoln Laboratory Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Kellis, Manolis Ernst, Jason Regev, Aviv Gymrek, Melissa A. Coyne, Michael J. Hundreds of chromatin regulators (CRs) control chromatin structure and function by catalyzing and binding histone modifications, yet the rules governing these key processes remain obscure. Here, we present a systematic approach to infer CR function. We developed ChIP-string, a meso-scale assay that combines chromatin immunoprecipitation with a signature readout of 487 representative loci. We applied ChIP-string to screen 145 antibodies, thereby identifying effective reagents, which we used to map the genome-wide binding of 29 CRs in two cell types. We found that specific combinations of CRs colocalize in characteristic patterns at distinct chromatin environments, at genes of coherent functions, and at distal regulatory elements. When comparing between cell types, CRs redistribute to different loci but maintain their modular and combinatorial associations. Our work provides a multiplex method that substantially enhances the ability to monitor CR binding, presents a large resource of CR maps, and reveals common principles for combinatorial CR function. National Human Genome Research Institute (U.S.) Center of Excellence in Genome Science (Grant) Howard Hughes Medical Institute National Institutes of Health (U.S.). Pioneer Award Burroughs Wellcome Fund 2014-12-10T17:28:44Z 2014-12-10T17:28:44Z 2011-12 2011-07 Article http://purl.org/eprint/type/JournalArticle 00928674 1097-4172 http://hdl.handle.net/1721.1/92255 Ram, Oren, Alon Goren, Ido Amit, Noam Shoresh, Nir Yosef, Jason Ernst, Manolis Kellis, et al. “Combinatorial Patterning of Chromatin Regulators Uncovered by Genome-Wide Location Analysis in Human Cells.” Cell 147, no. 7 (December 2011): 1628–1639. © 2011 Elsevier Inc. https://orcid.org/0000-0001-8567-2049 https://orcid.org/0000-0002-6086-3903 en_US http://dx.doi.org/10.1016/j.cell.2011.09.057 Cell Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier |
| spellingShingle | Ram, Oren Goren, Alon Amit, Ido Shoresh, Noam Yosef, Nir Ernst, Jason Kellis, Manolis Issner, Robbyn Durham, Timothy Zhang, Xiaolan Donaghey, Julie Epstein, Charles B. Regev, Aviv Bernstein, Bradley E. Gymrek, Melissa A. Coyne, Michael J. Combinatorial Patterning of Chromatin Regulators Uncovered by Genome-wide Location Analysis in Human Cells |
| title | Combinatorial Patterning of Chromatin Regulators Uncovered by Genome-wide Location Analysis in Human Cells |
| title_full | Combinatorial Patterning of Chromatin Regulators Uncovered by Genome-wide Location Analysis in Human Cells |
| title_fullStr | Combinatorial Patterning of Chromatin Regulators Uncovered by Genome-wide Location Analysis in Human Cells |
| title_full_unstemmed | Combinatorial Patterning of Chromatin Regulators Uncovered by Genome-wide Location Analysis in Human Cells |
| title_short | Combinatorial Patterning of Chromatin Regulators Uncovered by Genome-wide Location Analysis in Human Cells |
| title_sort | combinatorial patterning of chromatin regulators uncovered by genome wide location analysis in human cells |
| url | http://hdl.handle.net/1721.1/92255 https://orcid.org/0000-0001-8567-2049 https://orcid.org/0000-0002-6086-3903 |
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