PXD017054

PXD017054 is an original dataset announced via ProteomeXchange.

Title	Chromatin accessibility promotes hematopoietic and leukemia stem cell activity
Description	Chromatin organization is a highly orchestrated process that influences gene expression, in part by modulating access of regulatory factors to DNA and nucleosomes. We found that the chromatin accessibility regulator HMGN1, a target of recurrent DNA copy gains in leukemia, controls myeloid differentiation. HMGN1 amplification was associated with increased accessibility, expression, and histone H3K27 acetylation of loci important for hematopoietic stem cell (HSC) function and AML, such as HoxA cluster genes. In vivo, HMGN1 overexpression was linked to decreased quiescence and increased HSC activity in bone marrow transplantation. HMGN1 overexpression also cooperated with the AML-ETO9a fusion oncoprotein to impair myeloid differentiation and enhance leukemia stem cell (LSC) activity. Inhibition of histone acetyltransferases CBP/p300 relieved the HMGN1-associated differentiation block. These data nominate factors that modulate chromatin accessibility as regulators of HSCs and LSCs and suggest that targeting HMGN1 or its downstream effects on histone acetylation could be therapeutically active in AML.
HostingRepository	PRIDE
AnnounceDate	2020-02-25
AnnouncementXML	Submission_2020-05-18_07:02:37.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Miguel Prado
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-01-10 02:32:21	ID requested
1	2020-02-24 23:39:10	announced
⏵ 2	2020-05-18 07:02:38	announced	2020-05-18: Updated publication reference for PubMed record(s): 32179749.

Cabal-Hierro L, van Galen P, Prado MA, Higby KJ, Togami K, Mowery CT, Paulo JA, Xie Y, Cejas P, Furusawa T, Bustin M, Long HW, Sykes DB, Gygi SP, Finley D, Bernstein BE, Lane AA, Chromatin accessibility promotes hematopoietic and leukemia stem cell activity. Nat Commun, 11(1):1406(2020) [pubmed]

submitter keyword: Chromatin, leukemia, AML, HMGN1

Daniel Finley
contact affiliation	Finley and Gygi lab Cell Biology Department Harvard Medical School US
contact email	daniel_finley@hms.harvard.edu
lab head
Miguel Prado
contact affiliation	Harvard Medical School
contact email	miguel_prado@hms.harvard.edu
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/2020/02/PXD017054

PRIDE project URI

• PRIDE
  1. PXD017054
     1. Label: PRIDE project
     2. Name: Chromatin accessibility promotes hematopoietic and leukemia stem cell activity