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

Stem Cell Reports
Ly-Sha EeThomas G Fazzio

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.

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Citations

Feb 2, 2018·Journal of Clinical Medicine·Alissa duPuy Guarnaccia, William Patrick Tansey
Nov 27, 2019·Structural Dynamics·Matthew L DennisThomas S Peat
Jun 6, 2019·Scientific Reports·Juliane Lüscher-FirzlaffBernhard Lüscher
Mar 7, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jiawen CaoDanyan Cao
Jul 21, 2021·Journal of Medicinal Chemistry·Xin ChenXiaoke Guo

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Methods Mentioned

BETA
affinity purification
immunoprecipitation
co-immunoprecipitation
coIPs
pull down
RNA-seq

Software Mentioned

PyMol

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