PXD043920

PXD043920 is an original dataset announced via ProteomeXchange.

Title	MLL-AF4 cooperates with PAF1 and FACT to drive high density enhancer interactions in leukemia
Description	Aberrant enhancer activation is a key mechanism driving oncogene expression in many cancers. While much is known about the regulation of larger chromosome domains in eukaryotes, the details of enhancer-promoter interactions remain poorly understood. Recent work suggests co-activators like BRD4 and Mediator have little impact on enhancer-promoter interactions. In leukemias controlled by the MLL-AF4 fusion protein, we use the ultra-high resolution technique Micro-Capture-C (MCC) to show that MLL-AF4 binding promotes broad, high-density regions of enhancer-promoter interactions at a subset of key targets. These enhancers are enriched for transcription elongation factors like PAF1C and FACT and loss of these factors abolishes enhancer-promoter contact. This work not only provides a new model for how MLL-AF4 is able to drive high levels of transcription at key genes in leukemia, but also suggests a more general model linking enhancer-promoter crosstalk and transcription elongation.
HostingRepository	PRIDE
AnnounceDate	2023-08-18
AnnouncementXML	Submission_2023-08-18_05:07:43.710.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD043920
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	ThomasMilne
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-19 09:09:50	ID requested
⏵ 1	2023-08-18 05:07:44	announced

10.6019/PXD043920;

submitter keyword: Leukemia,MLL-AF4

Thomas AMilne
contact affiliation	MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK
contact email	thomas.milne@imm.ox.ac.uk
lab head
ThomasMilne
contact affiliation	University of Oxford
contact email	thomas.milne@imm.ox.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD043920
     1. Label: PRIDE project
     2. Name: MLL-AF4 cooperates with PAF1 and FACT to drive high density enhancer interactions in leukemia