PXD012715

PXD012715 is an original dataset announced via ProteomeXchange.

Title	BRD4 IP MS in leukemia - MTHFD1 interaction with BRD4 links folate metabolism to transcriptional regulation
Description	The histone acetyl-reader BRD4 is an important regulator of chromatin structure and transcription, yet factors modulating its activity have remained elusive. Here we describe two complementary screens for genetic and physical interactors of BRD4, which converge on the folate pathway enzyme MTHFD1. We show that a fraction of MTHFD1 resides in the nucleus, where it is recruited to distinct genomic loci by direct interaction with BRD4. Inhibition of either BRD4 or MTHFD1 results in similar changes in nuclear metabolite composition and gene expression, and pharmacologic inhibitors of the two pathways synergize to impair cancer cell viability in vitro and in vivo. Our finding that MTHFD1 and other metabolic enzymes are chromatin-associated suggests a direct role for nuclear metabolism in the control of gene expression.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:52:52.165.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Richard Imre
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	methylthiolated residue; monohydroxylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-02-14 05:35:57	ID requested
1	2019-04-04 00:01:43	announced
2	2019-12-13 04:00:11	announced	2019-12-13: Updated publication reference for PubMed record(s): 31133746.
⏵ 3	2024-10-22 04:52:53	announced	2024-10-22: Updated project metadata.

10.1038/s41588-019-0413-z;

Sdelci S, Rendeiro AF, Rathert P, You W, Lin JG, Ringler A, Hofst, ä, tter G, Moll HP, G, ü, rtl B, Farlik M, Schick S, Klepsch F, Oldach M, Buphamalai P, Schischlik F, M, á, jek P, Parapatics K, Schmidl C, Schuster M, Penz T, Buckley DL, Hudecz O, Imre R, Wang SY, Maric HM, Kralovics R, Bennett KL, M, ü, ller AC, Mechtler K, Menche J, Bradner JE, Winter GE, Klavins K, Casanova E, Bock C, Zuber J, Kubicek S, MTHFD1 interaction with BRD4 links folate metabolism to transcriptional regulation. Nat Genet, 51(6):990-998(2019) [pubmed]

curator keyword: Biomedical

submitter keyword: leukemia, MTHFD1, complex,BRD4

Karl Mechtler
contact affiliation	Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), 1030 Vienna, Austria
contact email	karl.mechtler@imp.ac.at
lab head
Richard Imre
contact affiliation	IMBA - Institute of Molecular Biotechnology
contact email	imre@imp.ac.at
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/2019/04/PXD012715

PRIDE project URI

• PRIDE
  1. PXD012715
     1. Label: PRIDE project
     2. Name: BRD4 IP MS in leukemia - MTHFD1 interaction with BRD4 links folate metabolism to transcriptional regulation