Department of Molecular, Cell, and Cancer Biology; Graduate School of Biomedical Sciences, Interdisciplinary Graduate Program
Cancer Biology | Cell Biology | Molecular Biology
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.
Mbd3, NuRD, Wdr5, chromatin, differentiation
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Copyright © 2017 The Author(s)
DOI of Published Version
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
Stem cell reports
Ee L, McCannell KN, Tang Y, Fernandes N, Hardy WR, Green MR, Chu F, Fazzio TG. (2017). An Embryonic Stem Cell-Specific NuRD Complex Functions through Interaction with WDR5. Open Access Articles. https://doi.org/10.1016/j.stemcr.2017.04.020. Retrieved from https://escholarship.umassmed.edu/oapubs/3147
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.