PXD050622

PXD050622 is an original dataset announced via ProteomeXchange.

Title	Neuronal differentiation requires BRAT1 complex to remove REST from chromatin
Description	Repressor element-1 silencing transcription factor (REST) is required for mature neurons formation. REST dysregulation underlies a key mechanism of neurodegeneration associated with neurological disorders. However, the mechanisms leading to alterations of REST-mediated silencing of key neurogenesis genes are not known. Here we show that BRAT1, a gene linked to neurodegenerative diseases, is required for activation of REST-responsive genes during neuronal-differentiation. We find that INTS11 and INTS9 subunits of Integrator complex interact with BRAT1 as a distinct trimeric complex to activate critical neuronal genes during differentiation. BRAT1 depletion results in persistence of REST residence on critical neuronal genes disrupting the differentiation of NT2 cells into astrocytes and neural cells. We identified BRAT1 and INTS11 co-occupying the promoter region of these genes and pinpoint a role for BRAT1 in recruiting INTS11 to their promoters. Disease-causing mutations in BRAT1 diminish its association with INTS11/INTS9, linking the manifestation of disease phenotypes with a defect in transcriptional activation of key neuronal genes by BRAT1/INTS11/INTS9 complex.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_13:20:55.044.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sadat Dokaneheifard
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-14 09:37:06	ID requested
⏵ 1	2025-05-06 13:20:55	announced

Dokaneheifard S, Gomes Dos Santos H, Guiselle Valencia M, Arigela H, Edupuganti RR, Shiekhattar R, Neuronal differentiation requires BRAT1 complex to remove REST from chromatin. Proc Natl Acad Sci U S A, 121(23):e2318740121(2024) [pubmed]

10.1073/pnas.2318740121;

submitter keyword: Integrator, neuronal differentiation,BRAT1

Dr. Ramin Shiekhattar
contact affiliation	Department of Human Genetics, University of Miami, Miller School of Medicine, Sylvester Comprehensive Cancer Center, 1501 NW 10th Avenue, Miami, FL 33136, USA
contact email	rshiekhattar@miami.edu
lab head
Sadat Dokaneheifard
contact affiliation	Department of Human Genetics, Silvester Conprehensive Cancer Center,University of Miami, Miami, Florida, USA
contact email	sxd1062@med.miami.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/2025/05/PXD050622

PRIDE project URI

• PRIDE
  1. PXD050622
     1. Label: PRIDE project
     2. Name: Neuronal differentiation requires BRAT1 complex to remove REST from chromatin