Proteomics,Multiomics

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Mtf2 is a methylation-sensitive DNA-binding recruiter of Polycomb


ABSTRACT: Polycomb repression of gene expression is critical for development, with a pivotal role for trimethylation of lysine 27 of histone H3 (H3K27me3) deposited by Polycomb Repressive Complex 2 (PRC2). While the function and regulation of PRC2 have been extensively studied, the mechanism(s) by which it is recruited to specific genomic targets has remained largely elusive, in particular in vertebrates. Here we identify the PRC2-associated protein Mtf2 as a novel DNA methylation-sensitive PRC2 recruiter in mouse embryonic stem cells (mESCs). Mtf2 directly binds to DNA and is essential for recruitment of PRC2 both in vitro and in vivo. Genome-wide recruitment of the PRC2 catalytic subunit Ezh2 to genomic targets is drastically impaired in Mtf2 knock-out mESCs, resulting in largely reduced H3K27me3 deposition. Mtf2 selectively binds regions with high density of closely spaced unmethylated CpG-containing motifs with a locally unwound helical structure. This binding is dependent on one of the Mtf2 PHD domains, a protein domain shared among Pcl homologs, and an Mtf2-specific domain. The sequences bound by Mtf2 are enriched in PRC2-repressed CpG island-containing targets in zebrafish, Xenopus, mouse and human, suggesting that Mtf2-mediated PRC2 recruitment to unmethylated genomic regions is conserved among vertebrates.

OTHER RELATED OMICS DATASETS IN: GSE68087PRJNA281741PRJNA369274

INSTRUMENT(S): Orbitrap Fusion, Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Embryonic Stem Cell

SUBMITTER: Matteo Perino  

LAB HEAD: Gert Jan C Veenstra

PROVIDER: PXD005821 | Pride | 2018-05-07

REPOSITORIES: Pride

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Publications

MTF2 recruits Polycomb Repressive Complex 2 by helical-shape-selective DNA binding.

Perino Matteo M   van Mierlo Guido G   Karemaker Ino D ID   van Genesen Siebe S   Vermeulen Michiel M   Marks Hendrik H   van Heeringen Simon J SJ   Veenstra Gert Jan C GJC  

Nature genetics 20180528 7


<h4>Abstact</h4>Polycomb-mediated repression of gene expression is essential for development, with a pivotal role played by trimethylation of histone H3 lysine 27 (H3K27me3), which is deposited by Polycomb Repressive Complex 2 (PRC2). The mechanism by which PRC2 is recruited to target genes has remained largely elusive, particularly in vertebrates. Here we demonstrate that MTF2, one of the three vertebrate homologs of Drosophila melanogaster Polycomblike, is a DNA-binding, methylation-sensitive  ...[more]

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