PXD072033-1

PXD072033 is an original dataset announced via ProteomeXchange.

Title	A distal activin-responsive super-enhancer regulates Fshb transcription and gonadotrope differentiation
Description	A large “gene desert” located far upstream from Fshb and Kcna4 contains several gonadotrope-specific accessible chromatin sites which, in chromatin conformation capture (3C), were seen to make distinct contacts with both genes. The region displays several features of a super-enhancer and both genes were strongly suppressed by JQ-1, which represses super-enhancer activity. The sites of open chromatin were seen, in chromatin immunoprecipitation (ChIP), to bind Brd4 and Med1, most notably at a site located -67 kb from the Fshb gene, as well as binding Ctcf further upstream (at -123 kbp), all of which were increased following activin exposure. The locus is also transcribed to chromatin-associated lncRNAs whose levels correlate with Fshb and Kcna4 mRNA levels in vivo and in cultured gonadotrope cells, indicating coordinated regulation. CRISPR interference (CRISPRi) confirmed distinct functions for each of the elements on these genes and, together with the 3C data, indicate that the -67 kb locus mediates specifically both basal and activin-stimulated Fshb expression, while the site at -59 kb contributes to activin-stimulation of both genes. Single-cell multiomics showed that the -67 kb element is accessible in pituitary stem cells and during gonadotrope differentiation, preceding opening of the Fshb promoter, although it is closed in other differentiated cell types. Foxl2 was found to bind this element and contributes to maintaining its chromatin accessibility, seemingly by recruiting Supt16H, a component of the FACT complex, with which it interacts. These findings define a distal, activin-responsive super-enhancer that regulates Fshb transcription and shapes the gonadotrope regulatory landscape.
HostingRepository	PRIDE
AnnounceDate	2026-04-27
AnnouncementXML	Submission_2026-04-26_16:22:02.405.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dganit Melamed Kadosh
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-12-15 23:24:48	ID requested
⏵ 1	2026-04-26 16:22:03	announced

Refael T, Golan G, Darsa D, Pnueli L, Chakravarty P, Rizzoti K, Melamed P, Accessibility at a primed distal Fshb-Kcna4 super-enhancer is facilitated by Foxl2 during gonadotrope differentiation. Endocrinology, 167(5):(2026) [pubmed]

10.1210/endocr/bqag028;

submitter keyword: activin,Fsh, gonadotrope differentiation

Philippa Melamed
contact affiliation	faculty of biology, Technion, Haifa, Israel
contact email	philippa@technion.ac.il
lab head
Dganit Melamed Kadosh
contact affiliation	Technion
contact email	sdganit@tx.technion.ac.il
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD072033
     1. Label: PRIDE project
     2. Name: A distal activin-responsive super-enhancer regulates Fshb transcription and gonadotrope differentiation