PXD038128

PXD038128 is an original dataset announced via ProteomeXchange.

Title	Glucose modulates transcription factor dimerization to enable tissue differentiation
Description	Glucose is a universal energy currency for living organisms, however, its non-energetic functions in processes such as differentiation are undefined. In epidermis, differentiating cells exhibit dynamic changes in gene expression1-4 driven by specific transcription factors (TFs)5-9. The interplay between such TFs and biomolecules that also change in this process is not understood. Metabolomic analyses revealed that increased intracellular glucose accompanies differentiation of epidermal keratinocytes. This elevation also occurred in differentiating cells from other tissues and was verified in epidermal tissue engineered with glucose sensors, which detected a glucose gradient that peaked in the outermost differentiated layers. Free glucose accumulation, unaccompanied by its increased metabolism, was essential for epidermal differentiation and required GLUT1, GLUT3, and SGLT1 transporters. Glucose affinity chromatography and azido-glucose click chemistry uncovered glucose binding to diverse regulatory proteins, including the IRF6 TF, whose epidermal knockout confirmed its requirement in glucose-dependent differentiation. Direct glucose binding enabled IRF6 dimerization, DNA binding, genomic localization, and induction of IRF6 target genes, including essential pro-differentiation TFs GRHL1, GRHL3, HOPX and PRDM1. The IRF6R84C mutant found in poorly differentiated cancers was unable to bind glucose. These data identify an essential new role for glucose as a modulator of protein multimerization in cellular differentiation.
HostingRepository	PRIDE
AnnounceDate	2025-03-13
AnnouncementXML	Submission_2025-03-13_12:18:09.728.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD038128
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Vanessa Lopez-Pajares
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-11-14 01:31:49	ID requested
⏵ 1	2025-03-13 12:18:10	announced

10.6019/PXD038128;

10.1016/J.STEM.2025.02.017;

submitter keyword: Differentiation,Metabolomics, Glucose, IRF6

Paul Khavari
contact affiliation	Stanford
contact email	Khavari@stanford.edu
lab head
Vanessa Lopez-Pajares
contact affiliation	Stanford University
contact email	vlopezp@stanford.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/2025/03/PXD038128

PRIDE project URI

• PRIDE
  1. PXD038128
     1. Label: PRIDE project
     2. Name: Glucose modulates transcription factor dimerization to enable tissue differentiation