PXD050989

PXD050989 is an original dataset announced via ProteomeXchange.

Title	Conserved helical motifs in the Ikaros IDR mediate NuRD interaction and transcriptional repression
Description	The transcription factor IKZF1/Ikaros is essential for B cell development, and recurrently mutated in human B-ALL. Ikaros has been ascribed both activating and repressive functions via interactions with coactivator and corepressor complexes, but the relative abundance of Ikaros-associated coregulatory complexes and their contribution to Ikaros-mediated gene regulation are not well understood. To address this issue, we performed an unbiased identification of Ikaros-interacting proteins in pre-B cells, and found that Ikaros interacts overwhelmingly with corepressors and heterochromatin-associated proteins. Time-resolved analysis of transcription and chromatin state identified transcriptional repression as the immediate response to Ikaros induction. Transcriptional repression preceded transcriptional activation by several hours, and was accompanied by a rapid loss of chromatin accessibility and reduced levels of H3K27ac particularly at enhancers. Functional characterisation of intrinsically disordered regions in the Ikaros protein identified highly conserved helical motifs that mediate Ikaros association with the NuRD corepressor complex and contribute to the silencing of target genes in pre-B cells and antiproliferative functions of Ikaros in human B-ALL
HostingRepository	PRIDE
AnnounceDate	2024-10-23
AnnouncementXML	Submission_2024-10-23_07:49:45.963.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alex Montoya
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	2-pyrrolidone-5-carboxylic acid (Gln); acetylated residue; monohydroxylated residue; deamidated residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-26 08:55:20	ID requested
⏵ 1	2024-10-23 07:49:46	announced

10.1182/BLOOD.2024024787;

submitter keyword: NuRD, corepressors,Ikaros, ikzf1, coactivators, chromatin

Dr Pavel Shliaha
contact affiliation	Head Proteomics and Metabolomics Core Facility
contact email	pavel.shliaha@lms.mrc.ac.uk
lab head
Alex Montoya
contact affiliation	Medical Research Council - London Institute of Medical Sciences
contact email	alex.montoya@lms.mrc.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD050989
     1. Label: PRIDE project
     2. Name: Conserved helical motifs in the Ikaros IDR mediate NuRD interaction and transcriptional repression