H2A.Z landscapes and dual modifications in pluripotent and multipotent stem cells underlie complex genome regulatory functions

Abstract Background The histone variant H2A.Z has been implicated in nucleosome exchange, transcriptional activation and Polycomb repression. However, the relationships among these seemingly disparate functions remain obscure. Results We mapped H2A.Z genome-wide in mammalian ES cells and neural prog...

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Main Authors: Ku, Manching, Rheinbay, Esther, Endoh, Mitsuhiro, Koseki, Haruhiko, Koche, Richard Patrick, Jaffe, Jacob D., Carr, Steven A., Bernstein, Bradley E.
Other Authors: Harvard University--MIT Division of Health Sciences and Technology
Format: Article
Language:English
Published: BioMed Central Ltd 2012
Online Access:http://hdl.handle.net/1721.1/73623
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author Ku, Manching
Rheinbay, Esther
Endoh, Mitsuhiro
Koseki, Haruhiko
Koche, Richard Patrick
Jaffe, Jacob D.
Carr, Steven A.
Bernstein, Bradley E.
author2 Harvard University--MIT Division of Health Sciences and Technology
author_facet Harvard University--MIT Division of Health Sciences and Technology
Ku, Manching
Rheinbay, Esther
Endoh, Mitsuhiro
Koseki, Haruhiko
Koche, Richard Patrick
Jaffe, Jacob D.
Carr, Steven A.
Bernstein, Bradley E.
author_sort Ku, Manching
collection MIT
description Abstract Background The histone variant H2A.Z has been implicated in nucleosome exchange, transcriptional activation and Polycomb repression. However, the relationships among these seemingly disparate functions remain obscure. Results We mapped H2A.Z genome-wide in mammalian ES cells and neural progenitors. H2A.Z is deposited promiscuously at promoters and enhancers, and correlates strongly with H3K4 methylation. Accordingly, H2A.Z is present at poised promoters with bivalent chromatin and at active promoters with H3K4 methylation, but is absent from stably repressed promoters that are specifically enriched for H3K27 trimethylation. We also characterized post-translational modification states of H2A.Z, including a novel species dually-modified by ubiquitination and acetylation that is enriched at bivalent chromatin. Conclusions Our findings associate H2A.Z with functionally distinct genomic elements, and suggest that post-translational modifications may reconcile its contrasting locations and roles.
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spelling mit-1721.1/736232022-09-26T13:28:38Z H2A.Z landscapes and dual modifications in pluripotent and multipotent stem cells underlie complex genome regulatory functions Ku, Manching Rheinbay, Esther Endoh, Mitsuhiro Koseki, Haruhiko Koche, Richard Patrick Jaffe, Jacob D. Carr, Steven A. Bernstein, Bradley E. Harvard University--MIT Division of Health Sciences and Technology Koche, Richard Patrick Abstract Background The histone variant H2A.Z has been implicated in nucleosome exchange, transcriptional activation and Polycomb repression. However, the relationships among these seemingly disparate functions remain obscure. Results We mapped H2A.Z genome-wide in mammalian ES cells and neural progenitors. H2A.Z is deposited promiscuously at promoters and enhancers, and correlates strongly with H3K4 methylation. Accordingly, H2A.Z is present at poised promoters with bivalent chromatin and at active promoters with H3K4 methylation, but is absent from stably repressed promoters that are specifically enriched for H3K27 trimethylation. We also characterized post-translational modification states of H2A.Z, including a novel species dually-modified by ubiquitination and acetylation that is enriched at bivalent chromatin. Conclusions Our findings associate H2A.Z with functionally distinct genomic elements, and suggest that post-translational modifications may reconcile its contrasting locations and roles. 2012-10-04T19:58:50Z 2012-10-04T19:58:50Z 2012-10 2012-07 2012-10-03T19:13:32Z Article http://purl.org/eprint/type/JournalArticle 1465-6906 1474-7596 http://hdl.handle.net/1721.1/73623 Genome Biology. 2012 Oct 03;13(10):R85 en http://dx.doi.org/10.1186/gb-2012-13-10-r85 Genome Biology Creative Commons Attribution http://creativecommons.org/licenses/by/2.0 Manching Ku et al.; licensee BioMed Central Ltd. application/pdf BioMed Central Ltd BioMed Central Ltd
spellingShingle Ku, Manching
Rheinbay, Esther
Endoh, Mitsuhiro
Koseki, Haruhiko
Koche, Richard Patrick
Jaffe, Jacob D.
Carr, Steven A.
Bernstein, Bradley E.
H2A.Z landscapes and dual modifications in pluripotent and multipotent stem cells underlie complex genome regulatory functions
title H2A.Z landscapes and dual modifications in pluripotent and multipotent stem cells underlie complex genome regulatory functions
title_full H2A.Z landscapes and dual modifications in pluripotent and multipotent stem cells underlie complex genome regulatory functions
title_fullStr H2A.Z landscapes and dual modifications in pluripotent and multipotent stem cells underlie complex genome regulatory functions
title_full_unstemmed H2A.Z landscapes and dual modifications in pluripotent and multipotent stem cells underlie complex genome regulatory functions
title_short H2A.Z landscapes and dual modifications in pluripotent and multipotent stem cells underlie complex genome regulatory functions
title_sort h2a z landscapes and dual modifications in pluripotent and multipotent stem cells underlie complex genome regulatory functions
url http://hdl.handle.net/1721.1/73623
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