PXD023993

PXD023993 is an original dataset announced via ProteomeXchange.

Title	A proteomics study identifying interactors of the FSHD2 gene product SMCHD1 reveals RUVBL1-dependent DUX4 repression.
Description	Structural Maintenance of Chromosomes Hinge Domain Containing 1 (SMCHD1) is a chromatin repressor, which is mutated in >95% of Facioscapulohumeral dystrophy (FSHD) type 2 cases. In FSHD2, SMCHD1 mutations ultimately result in the presence of the cleavage stage transcription factor DUX4 in muscle cells due to a failure in epigenetic repression of the D4Z4 macrosatellite repeat on chromosome 4q, which contains the DUX4 locus. While binding of SMCHD1 to D4Z4 and its necessity to maintain a repressive D4Z4 chromatin structure are well documented, it is unclear how SMCHD1 is recruited to D4Z4, and how it exerts its repressive properties on the chromatin. Here, we employ a quantitative proteomics approach to identify and characterize novel SMCHD1 interacting proteins, and assess their functionality in D4Z4 repression. We identify 47 robust SMCHD1 interactors, of which 19 are present in D4Z4 chromatin. We demonstrate that one of these SMCHD1 interacting proteins in D4Z4, RuvB-like 1 (RUVBL1) is indeed required for maintaining DUX4 silencing in FSHD myocytes. We also confirm the interaction of SMCHD1 with EZH inhibitory protein (EZHIP), which prevents global H3K27me3 deposition by the Polycomb repressive complex PRC2, providing novel insights into the potential function of SMCHD1 in the repression of DUX4 in the early stages of embryogenesis. The SMCHD1 interactome outlined herein can thus provide further direction into research on the potential function of SMCHD1 at genomic loci where SMCHD1 is known to act, such as D4Z4 repeats, the inactive X chromosome, autosomal gene clusters, imprinted loci and telomeres.
HostingRepository	PRIDE
AnnounceDate	2021-12-21
AnnouncementXML	Submission_2021-12-21_15:25:04.287.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Román González-Prieto
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-02-04 07:24:44	ID requested
⏵ 1	2021-12-21 15:25:05	announced

Goossens R, Tihaya MS, van den Heuvel A, Tabot-Ndip K, Willemsen IM, Tapscott SJ, Gonz, á, lez-Prieto R, Chang JG, Vertegaal ACO, Balog J, van der Maarel SM, A proteomics study identifying interactors of the FSHD2 gene product SMCHD1 reveals RUVBL1-dependent DUX4 repression. Sci Rep, 11(1):23642(2021) [pubmed]

submitter keyword: SMCHD1

FSHD

RUVBL1

SILAC

EZHIP

Alfred C.O. Vertegaal
contact affiliation	Cell and Chemical Biology Leiden University Medical Center, LUMC The Netherlands
contact email	vertegaal@lumc.nl
lab head
Román González-Prieto
contact affiliation	Leiden University Medical Center (LUMC)
contact email	R.Gonzalez_Prieto@lumc.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/2021/12/PXD023993

PRIDE project URI

• PRIDE
  1. PXD023993
     1. Label: PRIDE project
     2. Name: A proteomics study identifying interactors of the FSHD2 gene product SMCHD1 reveals RUVBL1-dependent DUX4 repression.