ArticleEndocrinology2011
Mutant Forkhead L2 (FOXL2) proteins associated with premature ovarian failure (POF) dimerize with wild-type FOXL2, leading to altered regulation of genes associated with granulosa cell differentiation.
Article in Endocrinology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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.
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Who cites it
19 citing papers in PubMed, 79 citations in OpenAlex.
- Modification of the Transcription Factor FOXL2 at Serines 101 and 107 Disables DNA Binding, Leads to Nucleolar Relocalization, and Rewires Granulosa-Cell Programs.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Single-cell transcriptomes of zebrafish germline reveal progenitor types and feminization by Foxl2l.eLife · 2025Article
- miR-6881-3p contributes to diminished ovarian reserve by regulating granulosa cell apoptosis by targeting SMAD4.Reproductive biology and endocrinology : RB&E · 2024Article
- Comparative Studies on DuplicatedGenes · 2023Article
- Next-generation sequencing of 500 POI patients identified novel responsible monogenic and oligogenic variants.Journal of ovarian research · 2023Article
- Identification and functional analyses of a novelInternational journal of ophthalmology · 2023Article
- Ovarian Reserve and ART Outcomes in Blepharophimosis-Ptosis-Epicanthus Inversus Syndrome Patients WithFrontiers in endocrinology · 2022Article
- lncRNAMolecular therapy. Nucleic acids · 2021Article
- A novel FOXL2 mutation in two infertile patients with blepharophimosis-ptosis-epicanthus inversus syndrome.Journal of assisted reproduction and genetics · 2020Article
- FOXL2C134W-Induced CYP19 Expression via Cooperation With SMAD3 in HGrC1 Cells.Endocrinology · 2018Article
- Parabens Accelerate Ovarian Dysfunction in a 4-Vinylcyclohexene Diepoxide-Induced Ovarian Failure Model.International journal of environmental research and public health · 2017Article
- Functional Analysis of a Novel FOXL2 Indel Mutation in Chinese Families with Blepharophimosis-Ptosis-Epicanthus Inversus Syndrome Type I.International journal of biological sciences · 2017Article
- Novel action of FOXL2 as mediator of Col1a2 gene autoregulation.Developmental biology · 2016Article
- Novel WT1 Missense Mutations in Han Chinese Women with Premature Ovarian Failure.Scientific reports · 2015Article
- Granulosa cell-derived induced pluripotent stem cells exhibit pro-trophoblastic differentiation potential.Stem cell research & therapy · 2015Article
- MCM9 mutations are associated with ovarian failure, short stature, and chromosomal instability.American journal of human genetics · 2014Article
- Exposure to chemical cocktails before or after conception--- the effect of timing on ovarian development.Molecular and cellular endocrinology · 2013Article
- Impaired fertility and FSH synthesis in gonadotrope-specific Foxl2 knockout mice.Molecular endocrinology (Baltimore, Md.) · 2013Article
- Minireview: roles of the forkhead transcription factor FOXL2 in granulosa cell biology and pathology.Endocrinology · 2011Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Premature ovarian failure in the autosomal dominant disorder blepharophimosis-ptosis-epicanthus inversus is due to mutations in the gene encoding Forkhead L2 (FOXL2), producing putative truncated proteins. We previously demonstrated that FOXL2 is a transcriptional repressor of the steroidogenic acute regulatory (StAR), P450SCC (CYP11A), P450aromatase (CYP19), and cyclin D2 (CCND2) genes, markers of ovarian follicle proliferation and differentiation. Furthermore, we found that mutations of FOXL2 may regulate wild-type FOXL2, leading to loss of transcriptional repression of CYP19, similar to StAR. However, the regulatory mechanisms underlying these premature ovarian failure-associated mutations remain largely unknown. Therefore, we examined the effects of a FOXL2 mutant protein on the transcriptional repression of the CYP19 promoter by the full-length protein. We found that mutant FOXL2 exerts a dominant-negative effect on the repression of CYP19 by wild-type FOXL2. Both wild-type and mutant FOXL2 and can form homo- and heterodimers. We identified a minimal -57-bp human CYP19 promoter containing two potential FOXL2-binding regions and found that both wild-type and mutant FOXL2 can bind to either of these regions. Mutational analysis revealed that either site is sufficient for transcriptional repression by wild-type FOXL2, and the dominant-negative effect of mutant FOXL2, but these are eliminated when both sites are mutated. These findings confirm that mutant FOXL2 exerts a dominant-negative effect on wild-type FOXL2's activity as a transcriptional repressor of key genes in ovarian follicle differentiation and suggest that this is likely due to heterodimer formation and possibly also competition for DNA binding.
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Registered trials
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