PXD029361

PXD029361 is an original dataset announced via ProteomeXchange.

Title	TWIST1 methylation by SETD6 selectively antagonizes LINC-PINT expression in Glioblastoma multiforme
Description	Glioblastoma multiforme (GBM) is the most common and aggressive malignant brain tumor among adults, which is characterized by high invasion, migration and proliferation abilities. One important process that contributes to the invasiveness of GBM is the epithelial to mesenchymal transition (EMT). EMT is regulated by a set of defined transcription factors which tightly regulate this process, among them is the basic helix-loop-helix family member, TWIST1. Here we show that TWIST1 is methylated on lysine-33 at chromatin by SETD6, a methyltransferase with expression levels correlating with poor survival in GBM patients. RNA-seq analysis in U251 GBM cells suggested that both SETD6 and TWIST1 regulate cell adhesion and migration processes. We further show that TWIST1 methylation attenuates the expression of the long-non-coding RNA, LINC-PINT, thereby suppressing EMT in GBM. Mechanistically, TWIST1 methylation represses the transcription of LINC-PINT by increasing the occupancy of EZH2 and the catalysis of the repressive H3K27me3 mark at the LINC-PINT locus. Under un-methylated conditions, TWIST1 dissociates from the LINC-PINT locus, allowing the expression of LINC-PINT which leads to increased cell adhesion and decreased cell migration. Together, our findings unravel a new mechanistic dimension for selective expression of LINC-PINT mediated by TWIST1 methylation.
HostingRepository	PRIDE
AnnounceDate	2022-08-12
AnnouncementXML	Submission_2022-08-11_23:19:51.979.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD029361
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	David Morgenstern
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monomethylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-10-26 07:00:51	ID requested
⏵ 1	2022-08-11 23:19:52	announced

Admoni-Elisha L, Elbaz T, Chopra A, Shapira G, Bedford MT, Fry CJ, Shomron N, Biggar K, Feldman M, Levy D, TWIST1 methylation by SETD6 selectively antagonizes LINC-PINT expression in glioma. Nucleic Acids Res, 50(12):6903-6918(2022) [pubmed]

submitter keyword: Glioblastoma, Methylation, SETD6, methyltransferase

Dan Levy
contact affiliation	The Shraga Segal Department of Microbiology, Immunology and Genetics,National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, P.O.B. 653, Be'er-Sheva 84105, Israel
contact email	ledan@post.bgu.ac.il
lab head
David Morgenstern
contact affiliation	Weizmann institute
contact email	david.morgenstern@weizmann.ac.il
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD029361
     1. Label: PRIDE project
     2. Name: TWIST1 methylation by SETD6 selectively antagonizes LINC-PINT expression in Glioblastoma multiforme