PXD027740-1

PXD027740 is an original dataset announced via ProteomeXchange.

Title	Enhancer recruitment of transcription repressors RUNX1 and TLE3 by mis-expressed FOXC1 blocks differentiation in acute myeloid leukemia
Description	Despite 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.
HostingRepository	PRIDE
AnnounceDate	2021-08-09
AnnouncementXML	Submission_2021-08-09_02:16:30.606.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Evangelia Papachristou
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; deamidated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-08-05 08:59:56	ID requested
⏵ 1	2021-08-09 02:16:30	announced

Dataset with its publication pending

submitter keyword: Acute myeloid leukemia, FOXC1, RUNX1, TLE3, Groucho

Tim Somervaille
contact affiliation	Leukaemia Biology Laboratory, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, M20 4GJ, United Kingdom;
contact email	tim.somervaille@cruk.manchester.ac.uk
lab head
Evangelia Papachristou
contact affiliation	Senior Scientific Assistant
contact email	Eva.Papachristou@cruk.cam.ac.uk
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/2021/08/PXD027740

PRIDE project URI

• PRIDE
  1. PXD027740
     1. Label: PRIDE project
     2. Name: Enhancer recruitment of transcription repressors RUNX1 and TLE3 by mis-expressed FOXC1 blocks differentiation in acute myeloid leukemia