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

First Author  Perino M Year  2018
Journal  Nat Genet Volume  50
Issue  7 Pages  1002-1010
PubMed ID  29808031 Mgi Jnum  J:268195
Mgi Id  MGI:6269610 Doi  10.1038/s41588-018-0134-8
Citation  Perino M, et al. (2018) MTF2 recruits Polycomb Repressive Complex 2 by helical-shape-selective DNA binding. Nat Genet 50(7):1002-1010
abstractText  ABSTACT: 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 PRC2 recruiter in mouse embryonic stem cells. 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 is abrogated in Mtf2 knockout cells, resulting in greatly reduced H3K27me3 deposition. MTF2 selectively binds regions with a high density of unmethylated CpGs in a context of reduced helix twist, which distinguishes target from non-target CpG islands. These results demonstrate instructive recruitment of PRC2 to genomic targets by MTF2.
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