PXD076443-1

PXD076443 is an original dataset announced via ProteomeXchange.

Title	The H3K4 methyltransferase KMT2D is an essential cofactor for GATA1 at erythroid gene enhancers
Description	Gene expression during cellular differentiation is coordinated by combinatorial interactions between transcription factors (TFs) and cofactors at promoters and enhancers. The “master TF” GATA1 coordinates gene transcription in a subset of hematopoietic lineages, including erythroid, megakaryocytic, mast, and eosinophil, while repressing the development of other blood lineages. However, the specific cofactors required for GATA1-activated gene expression during hematopoiesis are incompletely defined. We identified the cofactor KMT2D, an H3K4 methyltransferase that collaborates with H3K27 acetyltransferases to activate transcription, in an unbiased CRISPR/Cas9 screen for epigenetic regulators of erythropoiesis. Loss of KMT2D in human erythroid precursors caused developmental arrest with impaired expression of numerous erythroid genes. Mechanistically, KMT2D colocalized with GATA1 on more than one thousand erythroid enhancers associated with over two hundred erythroid genes. In general, co-occupancy of GATA1 and KMT2D at erythroid enhancers was associated with stronger transcriptional activity than occupancy by GATA1 alone. Acute depletion of KMT2D in erythroid precursors caused rapid reductions of H3K4me1 and H3K27ac on a subset of GATA1-bound enhancers and impaired the expression of canonical erythroid genes, including ZFPM1, SLC4A1, and EPOR. Moreover, acute depletion of GATA1 or KMT2D individually caused downregulation of overlapping gene sets. Thus, KMT2D controls erythropoiesis by selectively activating GATA1-dependent erythroid enhancers. Our studies identify KMT2D as a novel cofactor for transcriptional activation by GATA1 during erythropoiesis. More generally, our findings demonstrate how a lineage-specific TF cooperates with a ubiquitous epigenetic regulator to drive lineage-specific gene expression during cellular differentiation.
HostingRepository	PRIDE
AnnounceDate	2026-04-10
AnnouncementXML	Submission_2026-04-09_18:20:27.772.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ye Xin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2026-04-01 01:06:04	ID requested
⏵ 1	2026-04-09 18:20:28	announced

Dataset with its publication pending

submitter keyword: KMT2D

GATA1

enhancer

transcription regulation

hematopoiesis

erythropoiesis

epigenetics

Ye Xin
contact affiliation	Soochow university, China
contact email	20234053002@stu.suda.edu.cn
lab head
Ye Xin
contact affiliation	Soochow university
contact email	20234053002@stu.suda.edu.cn
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/2026/04/PXD076443

PRIDE project URI

• PRIDE
  1. PXD076443
     1. Label: PRIDE project
     2. Name: The H3K4 methyltransferase KMT2D is an essential cofactor for GATA1 at erythroid gene enhancers