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PXD012715

PXD012715 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleBRD4 IP MS in leukemia - MTHFD1 interaction with BRD4 links folate metabolism to transcriptional regulation
DescriptionThe 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.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:52:52.165.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterRichard Imre
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmethylthiolated residue; monohydroxylated residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-02-14 05:35:57ID requested
12019-04-04 00:01:43announced
22019-12-13 04:00:11announced2019-12-13: Updated publication reference for PubMed record(s): 31133746.
32024-10-22 04:52:53announced2024-10-22: Updated project metadata.
Publication List
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]
Keyword List
curator keyword: Biomedical
submitter keyword: leukemia, MTHFD1, complex,BRD4
Contact List
Karl Mechtler
contact affiliationResearch Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), 1030 Vienna, Austria
contact emailkarl.mechtler@imp.ac.at
lab head
Richard Imre
contact affiliationIMBA - Institute of Molecular Biotechnology
contact emailimre@imp.ac.at
dataset submitter
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Dataset FTP location
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PRIDE project URI
Repository Record List
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