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PXD027740-1

PXD027740 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleEnhancer recruitment of transcription repressors RUNX1 and TLE3 by mis-expressed FOXC1 blocks differentiation in acute myeloid leukemia
DescriptionDespite absent expression in normal hematopoiesis, the Forkhead factor FOXC1, a critical mesenchymal differentiation regulator, is highly expressed in ~30% of HOXAhigh AML to confer blocked monocyte/macrophage differentiation. Through integrated proteomics and bioinformatics, we discovered that FOXC1 and RUNX1 interact through Forkhead and Runt domains respectively and co occupy primed and active enhancers distributed close to differentiation genes. FOXC1 stabilises association of RUNX1, HDAC1 and Groucho repressor TLE3 to limit enhancer activity: FOXC1 knockdown induced loss of repressor proteins, gain of CEBPA binding, enhancer acetylation and upregulation of nearby genes, including KLF2. Furthermore, it triggered genome-wide redistribution of RUNX1, TLE3 and HDAC1 from enhancers to promoters leading to repression of self-renewal genes including MYC and MYB. Our studies highlight RUNX1 and CEBPA transcription factor swapping as a feature of leukemia cell differentiation, and reveal that FOXC1 prevents this by stabilising enhancer binding of a RUNX1/HDAC1/TLE3 transcription repressor complex, to oncogenic effect.
HostingRepositoryPRIDE
AnnounceDate2021-08-09
AnnouncementXMLSubmission_2021-08-09_02:16:30.606.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterEvangelia Papachristou
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; deamidated residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-08-05 08:59:56ID requested
12021-08-09 02:16:30announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Acute myeloid leukemia, FOXC1, RUNX1, TLE3, Groucho
Contact List
Tim Somervaille
contact affiliationLeukaemia Biology Laboratory, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, M20 4GJ, United Kingdom;
contact emailtim.somervaille@cruk.manchester.ac.uk
lab head
Evangelia Papachristou
contact affiliationSenior Scientific Assistant
contact emailEva.Papachristou@cruk.cam.ac.uk
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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