PXD005821

PXD005821 is an original dataset announced via ProteomeXchange.

Title	Mtf2 is a methylation-sensitive DNA-binding recruiter of Polycomb
Description	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.
HostingRepository	PRIDE
AnnounceDate	2018-05-07
AnnouncementXML	Submission_2018-06-07_00:13:53.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Matteo Perino
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-02-01 01:09:38	ID requested
1	2018-05-07 00:39:10	announced
⏵ 2	2018-06-07 00:13:54	announced	Updated publication reference for PubMed record(s): 29808031.

Perino M, van Mierlo G, Karemaker ID, van Genesen S, Vermeulen M, Marks H, van Heeringen SJ, Veenstra GJC, MTF2 recruits Polycomb Repressive Complex 2 by helical-shape-selective DNA binding. Nat Genet, 50(7):1002-1010(2018) [pubmed]

curator keyword: Biological

submitter keyword: Mtf2, Polycomb, Embryonic Stem Cells, PRC2

Gert Jan C Veenstra
contact affiliation	Radboud University, Department of Molecular Developmental Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, 6500 HB Nijmegen, The Netherlands
contact email	g.veenstra@science.ru.nl
lab head
Matteo Perino
contact affiliation	Radboud university
contact email	m.perino@science.ru.nl
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/05/PXD005821

PRIDE project URI

• PRIDE
  1. PXD005821
     1. Label: PRIDE project
     2. Name: Mtf2 is a methylation-sensitive DNA-binding recruiter of Polycomb