PXD030362

PXD030362 is an original dataset announced via ProteomeXchange.

Title	SMNDC1 links chromatin remodeling and splicing to regulate pancreatic hormone expression
Description	Insulin expression is restricted to the pancreatic beta cells, which are physically or functionally depleted in diabetes. Identifying targetable pathways repressing insulin in non-beta cells, particularly in the developmentally related glucagon-secreting alpha cells, is an important aim of regenerative medicine. Here, we performed an RNA interference screen in the murine alpha cell line, alphaTC1, to identify silencers of insulin expression. We discovered that knockdown of the splicing factor Smndc1 (Survival Motor Neuron Domain Containing 1) triggered a global repression of alpha cell gene-expression programs in favor of increased beta cell markers. Mechanistically, Smndc1 knockdown upregulated the key beta cell transcription factor Pdx1, by modulating the activities of the BAF and Atrx families of chromatin remodeling complexes. SMNDC1’s repressive role was conserved in human pancreatic islets, its loss triggering enhanced insulin secretion and PDX1 expression. Our study identifies Smndc1 as a key factor connecting splicing and chromatin remodeling to the control of insulin expression in human and mouse islet cells.
HostingRepository	PRIDE
AnnounceDate	2022-07-01
AnnouncementXML	Submission_2022-07-01_06:32:50.151.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Frédéric FONTAINE
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-12-13 07:04:26	ID requested
⏵ 1	2022-07-01 06:32:50	announced

Dataset with its publication pending

submitter keyword: Insulin transcription, pancreatic islets, RNAi screen, SMNDC1, chromatin remodelers, splicing, alpha cells, beta cells

Stefan Kubicek
contact affiliation	Kubicek lab, Principal Investigator, Head of Molecular Discovery Platform, CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
contact email	skubicek@cemm.oeaw.ac.at
lab head
Frédéric FONTAINE
contact affiliation	CeMM Research Center for Molecular Medicine
contact email	frederic.fontaine.pro@gmail.com
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/2022/07/PXD030362

PRIDE project URI

• PRIDE
  1. PXD030362
     1. Label: PRIDE project
     2. Name: SMNDC1 links chromatin remodeling and splicing to regulate pancreatic hormone expression