Evidence map›Paper›PMID 41717998›Full record

ArticleEndocrinology2026

Regulation of murine follicle-stimulating hormone β subunit transcription by newly identified enhancers.

Yangfan Jin, Hailey Schultz, Luisina Ongaro, Gauthier Schang, Xiang Zhou, Carlos Agustin Isidro Alonso, Michel Zamojski, German Nudelman, Natalia Mendelev, Shinsuke Onuma and 5 more

Abstract read
In one paragraph

Article in Endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Yangfan JinDepartment of Pharmacology and Therapeutics, McGill University, Montreal, QC H3G 1Y6, Canada.
Hailey SchultzDepartment of Anatomy and Cell Biology, McGill University, Montreal, QC H3G 1Y6, Canada.
Luisina OngaroDepartment of Pharmacology and Therapeutics, McGill University, Montreal, QC H3G 1Y6, Canada.ORCID 0000-0002-5449-2894
Gauthier SchangDepartment of Pharmacology and Therapeutics, McGill University, Montreal, QC H3G 1Y6, Canada.
Xiang ZhouDepartment of Pharmacology and Therapeutics, McGill University, Montreal, QC H3G 1Y6, Canada.
Carlos Agustin Isidro AlonsoDepartment of Pharmacology and Therapeutics, McGill University, Montreal, QC H3G 1Y6, Canada.
Michel ZamojskiDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
German NudelmanDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Natalia MendelevDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Shinsuke OnumaDepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Corrine K WeltDivision of Endocrinology, Metabolism and Diabetes, University of Utah, Salt Lake City, UT 84112, USA.
Louise M BilezikjianClayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Stuart C SealfonDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Frederique Ruf-ZamojskiDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Daniel J BernardDepartment of Pharmacology and Therapeutics, McGill University, Montreal, QC H3G 1Y6, Canada.ORCID 0000-0001-5365-5586

Funding

MOLECULAR MECHANISM OF AGONISM AT THE GNRH RECEPTORR01DK046943 · NIDDK · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI STUART C. SEALFON · 1993 to 2026
$11.0M
Regulation of Follistatin Expression by ActivinR01HD046941 · NICHD · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI BILEZIKJIAN, LOUISE M · 2004 to 2014
$3.5M
Primary Ovarian Insufficiency: Etiology and Comorbid DiseaseR01HD099487 · NICHD · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI CORRINE K WELT · 2019 to 2026
$2.7M
Integrated systems biology of the pituitaryR56DK046943 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI SEALFON, STUART C. · 2006 to 2024
$555k
Fonds de Recherche du Québec 31338Natural Sciences and Engineering Research CouncilNICHD NIH HHS R01 HD046941NICHD NIH HHS R01 HD099487NIDDK NIH HHS R01 DK046943NIDDK NIH HHS R56 DK046943NIH HHS 152308NIH HHS DK46943NIH HHS HD099487NIH HHS HD46941of Canada RGPIN-2023-04812
6 · The paper itself

Abstract

Activin-class ligands of the transforming growth factor β family induce follicle-stimulating hormone (FSH) production by pituitary gonadotrope cells in mice via the actions of the transcription factors SMAD3, SMAD4, and FOXL2, which bind to cis-elements in the FSHβ subunit (Fshb) promoter. An enhancer region for murine Fshb transcription was identified in vitro. However, deletion of the region using CRISPR-Cas9 did not affect FSH synthesis or secretion in mice. Using single-nucleus ATAC-seq of whole murine pituitaries, we identified 3 additional open chromatin regions upstream of Fshb exclusively in gonadotropes. These regions, as well as the Fshb gene, were fully or partially closed in gonadotropes of FSH-deficient mice with genetically or pharmacologically inactivated activin type II receptors. The initially characterized enhancer region did not significantly alter basal or activin-stimulated murine Fshb promoter-reporter activity in homologous LβT2 cells. In contrast, the other 3 open chromatin regions enhanced basal and activin A-stimulated Fshb promoter-reporter activity in LβT2 cells, with the 2 most distal showing the greatest effects. These 2 regions were open, exhibited enrichment of the enhancer mark H3K27ac, and were bound by SMAD2/3 and FOXL2 in response to activin A in LβT2 cells. The most distal enhancer exhibited strong FOXL2 and weak SMAD4 binding in gel shift assays. SMAD4, but not FOXL2, directly bound the other distal enhancer. Mutation of defined FOXL2 and SMAD4 cis-elements diminished enhancer activity in reporter assays in LβT2 cells. Collectively, the data indicate that there may be as many as 4 activin-sensitive enhancers upstream of murine Fshb.

Indexed as

Enhancer Elements, GeneticFollicle Stimulating Hormone, beta SubunitTranscription, GeneticActivinsAnimalsFemaleForkhead Box Protein L2Gene Expression RegulationGonadotrophsMiceMice, KnockoutPromoter Regions, GeneticSmad3 ProteinSmad4 ProteinActivinsFollicle Stimulating Hormone, beta SubunitForkhead Box Protein L2Foxl2 protein, mouseSmad3 ProteinSmad3 protein, mouseSmad4 ProteinSmad4 protein, mouseactivinFSHpituitaryreproductiontranscription

Identifiers

PMID41717998
PMCPMC13070615

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.