PXD054677

PXD054677 is an original dataset announced via ProteomeXchange.

Title	Maintenance of β-cell identity through the transcription co-factors TBL1X and TBL1XR1
Description	Diabetes occurs because of inadequate insulin secretion from pancreatic β-cells, relative to insulin requirements. One mechanism explaining β-cell malfunction in diabetes is their loss of identity, maintained by a series of well-defined transcription factors, which activate the transcription of β-cell genes including insulin, while repressing the transcription of “disallowed” genes. We have identified the transcriptional co-factors transducin β-like 1 x-linked (TBL1X) and its homolog TBL1X-related (TBL1XR1) as crucial regulators of β-cell identity and function, as β-cell specific knockout in mice leads to severe, progressive hypoinsulinemia and hyperglycemia. Single cell RNA sequencing showed loss of β-cells, gain of polyhormonal cells, and reduced β-cell maturity upon TBL/R knockout, indicative of dedifferentiated cells. Mechanistically, interactome screens and chromatin immunoprecipitation showed that TBL/R directly regulate insulin gene expression by forming a gene regulatory network with the islet cell master regulator paired box 6 (PAX6) and histone deacetylase 3 (HDAC3). Overall, our study provides evidence for an as yet unknown regulatory layer maintaining β-cell identity, relevant for development and progression of diabetes.
HostingRepository	PRIDE
AnnounceDate	2026-03-25
AnnouncementXML	Submission_2026-03-25_04:06:18.873.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stefanie Hauck
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-07 09:17:08	ID requested
⏵ 1	2026-03-25 04:06:19	announced

Dataset with its publication pending

submitter keyword: transcriptional control, TBL1XR1, cell identity,β-cells, differentiation, PAX6, TBL1X, insulin, diabetes

Maria Rohm
contact affiliation	Institute for Diabetes and Cancer (IDC), Helmholtz Diabetes Center, Helmholtz Center Munich, Neuherberg, Germany
contact email	maria.rohm@helmholtz-munich.de
lab head
Stefanie Hauck
contact affiliation	Research Unit Protein Science, Helmholtz Zentrum München
contact email	hauck@helmholtz-muenchen.de
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/2026/03/PXD054677

PRIDE project URI

• PRIDE
  1. PXD054677
     1. Label: PRIDE project
     2. Name: Maintenance of β-cell identity through the transcription co-factors TBL1X and TBL1XR1