An Embryonic Stem Cell-Specific NuRD Complex Functions through Interaction with WDR5

An Embryonic Stem Cell-Specific NuRD Complex Functions through Interaction with WDR5

The Nucleosome Remodeling and Deacetylase (NuRD) complex is a chromatin regulatory complex that functions as a transcriptional co-repressor in metazoans. The NuRD subunit MBD3 is essential for targeting and assembly of a functional NuRD complex as well as embryonic stem cell (ESC) pluripotency. Thre...

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Main Authors: Ly-Sha Ee, Kurtis N. McCannell, Yang Tang, Nancy Fernandes, W. Rod Hardy, Michael R. Green, Feixia Chu, Thomas G. Fazzio
Format: Article
Language:English
Published: Elsevier 2017-06-01
Series:Stem Cell Reports
Subjects:
NuRD
Mbd3
Wdr5
chromatin
differentiation
Online Access:http://www.sciencedirect.com/science/article/pii/S2213671117301741
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spelling doaj-f8e6ef562d6546779d980cf547c22c372020-11-24T22:35:07ZengElsevierStem Cell Reports2213-67112017-06-01861488149610.1016/j.stemcr.2017.04.020An Embryonic Stem Cell-Specific NuRD Complex Functions through Interaction with WDR5Ly-Sha Ee0Kurtis N. McCannell1Yang Tang2Nancy Fernandes3W. Rod Hardy4Michael R. Green5Feixia Chu6Thomas G. Fazzio7Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USADepartment of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USADepartment of Molecular, Cellular, and Biomedical Sciences, University of New Hampshire, Durham, NH 03824, USADepartment of Molecular, Cellular, and Biomedical Sciences, University of New Hampshire, Durham, NH 03824, USADepartment of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USADepartment of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USADepartment of Molecular, Cellular, and Biomedical Sciences, University of New Hampshire, Durham, NH 03824, USADepartment of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USAThe Nucleosome Remodeling and Deacetylase (NuRD) complex is a chromatin regulatory complex that functions as a transcriptional co-repressor in metazoans. The NuRD subunit MBD3 is essential for targeting and assembly of a functional NuRD complex as well as embryonic stem cell (ESC) pluripotency. Three MBD3 isoforms (MBD3A, MBD3B, and MBD3C) are expressed in mouse. Here, we find that the MBD3C isoform contains a unique 50-amino-acid N-terminal region that is necessary for MBD3C to specifically interact with the histone H3 binding protein WDR5. Domain analyses of WDR5 reveal that the H3 binding pocket is required for interaction with MBD3C. We find that while Mbd3c knockout ESCs differentiate normally, MBD3C is redundant with the MBD3A and MBD3B isoforms in regulation of gene expression, with the unique MBD3C N terminus required for this redundancy. Together, our data characterize a unique NuRD complex variant that functions specifically in ESCs.http://www.sciencedirect.com/science/article/pii/S2213671117301741NuRDMbd3Wdr5chromatindifferentiation
collection DOAJ
language English
format Article
sources DOAJ
author Ly-Sha Ee
Kurtis N. McCannell
Yang Tang
Nancy Fernandes
W. Rod Hardy
Michael R. Green
Feixia Chu
Thomas G. Fazzio
spellingShingle Ly-Sha Ee
Kurtis N. McCannell
Yang Tang
Nancy Fernandes
W. Rod Hardy
Michael R. Green
Feixia Chu
Thomas G. Fazzio
An Embryonic Stem Cell-Specific NuRD Complex Functions through Interaction with WDR5
Stem Cell Reports
NuRD
Mbd3
Wdr5
chromatin
differentiation
author_facet Ly-Sha Ee
Kurtis N. McCannell
Yang Tang
Nancy Fernandes
W. Rod Hardy
Michael R. Green
Feixia Chu
Thomas G. Fazzio
author_sort Ly-Sha Ee
title An Embryonic Stem Cell-Specific NuRD Complex Functions through Interaction with WDR5
title_short An Embryonic Stem Cell-Specific NuRD Complex Functions through Interaction with WDR5
title_full An Embryonic Stem Cell-Specific NuRD Complex Functions through Interaction with WDR5
title_fullStr An Embryonic Stem Cell-Specific NuRD Complex Functions through Interaction with WDR5
title_full_unstemmed An Embryonic Stem Cell-Specific NuRD Complex Functions through Interaction with WDR5
title_sort embryonic stem cell-specific nurd complex functions through interaction with wdr5
publisher Elsevier
series Stem Cell Reports
issn 2213-6711
publishDate 2017-06-01
description The Nucleosome Remodeling and Deacetylase (NuRD) complex is a chromatin regulatory complex that functions as a transcriptional co-repressor in metazoans. The NuRD subunit MBD3 is essential for targeting and assembly of a functional NuRD complex as well as embryonic stem cell (ESC) pluripotency. Three MBD3 isoforms (MBD3A, MBD3B, and MBD3C) are expressed in mouse. Here, we find that the MBD3C isoform contains a unique 50-amino-acid N-terminal region that is necessary for MBD3C to specifically interact with the histone H3 binding protein WDR5. Domain analyses of WDR5 reveal that the H3 binding pocket is required for interaction with MBD3C. We find that while Mbd3c knockout ESCs differentiate normally, MBD3C is redundant with the MBD3A and MBD3B isoforms in regulation of gene expression, with the unique MBD3C N terminus required for this redundancy. Together, our data characterize a unique NuRD complex variant that functions specifically in ESCs.
topic NuRD
Mbd3
Wdr5
chromatin
differentiation
url http://www.sciencedirect.com/science/article/pii/S2213671117301741
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