Mcm2 promotes stem cell differentiation via its ability to bind H3-H4
- Columbia University Medical Center, United States
- University of Colorado Denver, United States
Abstract
Mcm2, a subunit of the Mcm2-7 helicase best known for its role in DNA replication, contains a histone binding motif that facilitates the transfer of parental histones following DNA replication. Here we show that Mcm2 is important for the differentiation of mouse embryonic stem (ES) cells. The Mcm2-2A mutation defective in histone binding shows defects in silencing of pluripotent genes and the induction of lineage specific genes. The defects in the induction of lineage specific genes in the mutant cells are likely, at least in part, due to reduced binding to Asf1a, a histone chaperone that binds Mcm2 and is important for nucleosome disassembly at bivalent chromatin domains containing repressive H3K27me3 and active H3K4me3 modifications during differentiation. Mcm2 localizes at transcription starting sites and the binding of Mcm2 at gene promoters is disrupted in both Mcm2-2A ES cells and neuro-precursor cells (NPCs). Reduced Mcm2 binding at bivalent chromatin domains in Mcm2-2A ES cells correlates with decreased chromatin accessibility at corresponding sites in NPCs. Together, our studies reveal a novel function of Mcm2 in ES cell differentiation, likely through manipulating chromatin landscapes at bivalent chromatin domains.
Data availability
Raw and processed sequencing data generated in the course of this study can be accessed via the GEO database with accession number: GSE203272.
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Mcm2 promotes stem cell differentiation via its ability to bind H3-H4NCBI Gene Expression Omnibus, GSE203272.
Article and author information
Author details
Funding
National Institute of General Medical Sciences (R35118015)
- Zhiguo Zhang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2022, Xu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Mcm2 promotes stem cell differentiation via its ability to bind H3-H4
eLife 11:e80917.
https://doi.org/10.7554/eLife.80917
