PXD017657

PXD017657 is an original dataset announced via ProteomeXchange.

Title	Inactivation of the nuclear interacting SET domain protein 1 (NSD1) impairs GATA1-regulated erythroid differentiation and causes erythroleukemia
Description	Nuclear receptor binding SET domain protein 1 (NSD1) is recurrently mutated in human cancers including acute leukemia. We found that NSD1 knockdown altered erythroid clonogenic growth of human CD34+ hematopoietic cells. Ablation of Nsd1 in the hematopoietic system induced a transplantable erythroleukemia in mice. Despite abundant expression of the transcriptional master regulator GATA1, in vitro differentiation of Nsd1-/- erythroblasts was majorly impaired associated with reduced activation of GATA1-induced targets, while GATA1-repressed target genes were less affected. Retroviral expression of wildtype Nsd1, but not a catalytically-inactive Nsd1N1918Q SET-domain mutant induced terminal maturation of Nsd1-/- erythroblasts. Despite similar GATA1 levels, exogenous Nsd1 but not Nsd1N1918Q significantly increased GATA1 chromatin occupancy and target gene activation. Notably, Nsd1 expression reduced the association of GATA1 with the co-repressor SKI, and knockdown of SKI induced differentiation of Nsd1-/- erythroblasts. Collectively, we identified the NSD1 methyltransferase as a novel regulator of GATA1-controlled erythroid differentiation and leukemogenesis.
HostingRepository	PRIDE
AnnounceDate	2020-04-08
AnnouncementXML	Submission_2020-06-16_22:44:13.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD017657
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Thomas Bock
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	Oxidation; Acetyl; monohydroxylated residue; Carbamidomethyl; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2020-02-20 03:16:55	ID requested
1	2020-04-07 22:21:10	announced
⏵ 2	2020-06-16 22:44:13	announced	2020-06-17: Updated publication reference for PubMed record(s): 32533074.

Leonards K, Almosailleakh M, Tauchmann S, Bagger FO, Thirant C, Juge S, Bock T, M, é, reau H, Bezerra MF, Tzankov A, Ivanek R, Losson R, Peters AHFM, Mercher T, Schwaller J, Nuclear interacting SET domain protein 1 inactivation impairs GATA1-regulated erythroid differentiation and causes erythroleukemia. Nat Commun, 11(1):2807(2020) [pubmed]

submitter keyword: NSD1-erythroid differentiation-leukemia-GATA1-SKI

Alexander Schmidt
contact affiliation	University of Basel, Biozentrum, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland
contact email	alex.schmidt@unibas.ch
lab head
Thomas Bock
contact affiliation	Proteomics Core Facility, Biozentrum, University of Basel, Switzerland
contact email	thomas.bock@unibas.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD017657
     1. Label: PRIDE project
     2. Name: Inactivation of the nuclear interacting SET domain protein 1 (NSD1) impairs GATA1-regulated erythroid differentiation and causes erythroleukemia