UMMS Affiliation

Department of Molecular, Cell, and Cancer Biology; Graduate School of Biomedical Sciences, Interdisciplinary Graduate Program

Publication Date

2017-06-06

Document Type

Article

Disciplines

Cancer Biology | Cell Biology | Molecular Biology

Abstract

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.

Keywords

Mbd3, NuRD, Wdr5, chromatin, differentiation

Rights and Permissions

Copyright © 2017 The Author(s)

DOI of Published Version

10.1016/j.stemcr.2017.04.020

Source

Stem Cell Reports. 2017 Jun 6;8(6):1488-1496. doi: 10.1016/j.stemcr.2017.04.020. Epub 2017 May 18. Link to article on publisher's site

Journal/Book/Conference Title

Stem cell reports

Comments

First author Ly-Sha Ee is a doctoral student in the Interdisciplinary Graduate Program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.

Related Resources

Link to Article in PubMed

PubMed ID

28528697

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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