Affinage

FST

Follistatin · UniProt P19883

Length
344 aa
Mass
38.0 kDa
Annotated
2026-06-09
73 papers in source corpus 4 papers cited in narrative 4 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Follistatin (FST) acts as a negative regulator of ovarian follicle growth and granulosa cell function, where its knockdown increases granulosa cell proliferation and estrogen secretion and FSH treatment sharply downregulates its expression (PMID:27565874). In oocytes and cumulus cells, FST promotes in vitro oocyte maturation, cumulus expansion, and early embryonic (blastocyst) development, acting through the TGF-β/SMAD pathway by upregulating TGF-β, SMAD2, SMAD3, and the anti-apoptotic factor Bcl-2 while downregulating SMAD4 and BAX (PMID:37917549). FST transcription is directly activated by ERRβ, which binds the FST promoter and drives FST-mediated apoptosis and E-cadherin upregulation in breast cancer cells; ERRβ also indirectly represses FST via BCAS2-dependent downregulation of β-catenin/TCF4 recruitment to the FST promoter (PMID:24667650). Beyond reproductive and transcriptional contexts, FST overexpression suppresses myogenic regulators (PAX7, PAX3, MYOG, MYOD, MYF5) while inducing lipid-metabolism genes, linking it to muscle development and lipid handling (PMID:41153936).

Mechanistic history

Synthesis pass · year-by-year structured walk · 4 steps
  1. 2014 Medium

    Established how FST expression is controlled at the transcriptional level, identifying FST as a direct ERRβ target with both positive and indirect negative regulatory arms.

    Evidence ChIP cloning, gel supershift, Co-IP, and qRT-PCR in breast cancer cells

    PMID:24667650

    Open questions at the time
    • Functional consequences (apoptosis, E-cadherin) measured in a single lab without independent replication
    • Does not address FST's secreted ligand-binding activity
  2. 2016 Medium

    Defined FST as a negative regulator of follicle growth, showing it restrains granulosa cell proliferation and estrogen output downstream of FSH.

    Evidence siRNA knockdown with proliferation and estrogen secretion assays in porcine granulosa cells

    PMID:27565874

    Open questions at the time
    • Single study, single species
    • Molecular mechanism linking FST loss to proliferation not resolved
  3. 2023 Medium

    Connected FST to oocyte maturation and early embryo development, placing its action within the TGF-β/SMAD pathway and cumulus cell survival.

    Evidence siRNA knockdown and overexpression with maturation, mitochondrial localization, and parthenogenetic activation assays in buffalo follicles

    PMID:37917549

    Open questions at the time
    • Pathway inference rests on expression of SMAD genes, not direct SMAD activation readouts
    • Single lab
  4. 2025 Low

    Extended FST function beyond reproduction, implicating it in suppressing myogenic differentiation while promoting lipid metabolism in muscle satellite cells.

    Evidence Overexpression with RNA-seq and qRT-PCR validation in goose skeletal muscle satellite cells

    PMID:41153936

    Open questions at the time
    • Single overexpression experiment with no loss-of-function
    • No protein-level mechanistic validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • The direct molecular activity of FST as a secreted binding protein (e.g. its ligand targets and binding mechanism) is not characterized in the available corpus.
  • No structural or biochemical binding data in timeline
  • Cross-tissue mechanism (reproduction vs muscle) not unified by direct experiment

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 2
Pathway
R-HSA-1474165 Reproduction 2 R-HSA-162582 Signal Transduction 2

Evidence

Reading pass · 4 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 ERRβ transcriptionally activates FST in breast cancer cells; chromatin immunoprecipitation identified FST as a direct ERRβ transcriptional target. Overexpressed ERRβ induced FST-mediated apoptosis and enhanced E-cadherin expression through FST upregulation. Additionally, ERRβ-mediated upregulation of BCAS2 inhibited FST transcription by downregulating β-catenin/TCF4 recruitment to the FST promoter. ChIP cloning, gel supershift assay, co-immunoprecipitation, western blotting, confocal microscopy, qRT-PCR British journal of cancer Medium 24667650
2023 FST is expressed in buffalo ovarian follicles at multiple stages and during oocyte maturation; FST overexpression promoted in vitro oocyte maturation rate and blastocyst development. FST knockdown in cumulus cells caused abnormal mitochondrial localization, reduced cumulus expansion, and decreased cleavage/blastocyst rates after parthenogenetic activation. Mechanistically, FST overexpression upregulated Bcl-2, TGF-β, SMAD2, and SMAD3 while downregulating SMAD4 and BAX, indicating FST acts through the TGF-β/SMAD pathway to regulate oocyte maturation and cumulus cell apoptosis. siRNA knockdown, overexpression vector (pcDNA3.1-EGFP-FST), RT-qPCR, immunostaining, mitochondrial localization assay, parthenogenetic activation assay Reproduction in domestic animals Medium 37917549
2016 FST mRNA levels decreased from weaning to estrus in porcine ovary, and FSH treatment (250 ng/ml) sharply decreased FST expression in porcine granulosa cells. Knockdown of FST by siRNA significantly increased granulosa cell proliferation and estrogen secretion, establishing FST as a negative regulator of follicle growth and granulosa cell function. siRNA knockdown, real-time PCR, cell proliferation assay, estrogen secretion measurement Animal biotechnology Medium 27565874
2025 In goose skeletal muscle satellite cells (SMSCs), overexpression of FST downregulated stemness markers PAX7 and PAX3 and myogenic regulators (MYOG, MYOD, MYF5), while upregulating lipid metabolism genes (PPARG, FABP5, ACSL5) and myosin-related genes. Pathway analysis linked FST-regulated genes to TGF-β, PPAR, fatty acid metabolism, and Notch signaling pathways, indicating a dual regulatory role in skeletal muscle development and lipid metabolism. Overexpression in SMSCs, comparative transcriptome analysis (RNA-seq), qRT-PCR validation Animals Low 41153936

Source papers

Stage 0 corpus · 73 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Indirect measures of gene flow and migration: FST not equal to 1/(4Nm + 1). Heredity 700 10098262
2011 Comparison of F(ST) outlier tests for SNP loci under selection. Molecular ecology resources 305 21429174
2011 G'ST and D do not replace FST. Molecular ecology 175 21375616
2007 Divergent selection as revealed by P(ST) and QTL-based F(ST) in three-spined stickleback (Gasterosteus aculeatus) populations along a coastal-inland gradient. Molecular ecology 91 17284219
1991 FST in a hierarchical island model. Genetics 83 2016058
2016 Population-specific FST values for forensic STR markers: A worldwide survey. Forensic science international. Genetics 69 27082756
2013 Combined analyses of kinship and FST suggest potential drivers of chaotic genetic patchiness in high gene-flow populations. Molecular ecology 66 23802550
2011 Comparisons between Q(ST) and F(ST) --how wrong have we been? Molecular ecology 50 22060729
2007 Inferring local adaptation from QST-FST comparisons: neutral genetic and quantitative trait variation in European populations of great snipe. Journal of evolutionary biology 49 17584249
2006 Addiction toxin Fst has unique effects on chromosome segregation and cell division in Enterococcus faecalis and Bacillus subtilis. Journal of bacteriology 49 16855226
2019 Background selection and FST : Consequences for detecting local adaptation. Molecular ecology 48 31349365
2013 The antidepressant-like effect of inosine in the FST is associated with both adenosine A1 and A 2A receptors. Purinergic signalling 45 23613131
2014 ERRβ signalling through FST and BCAS2 inhibits cellular proliferation in breast cancer cells. British journal of cancer 41 24667650
2014 Activation of the mTOR signaling pathway in the antidepressant-like activity of the mGlu5 antagonist MTEP and the mGlu7 agonist AMN082 in the FST in rats. Neuropharmacology 40 24631968
2011 If F(ST) does not measure neutral genetic differentiation, then comparing it with Q(ST) is misleading. Or is it? Molecular ecology 40 21410574
2003 Enterococcus faecalis plasmid pAD1-encoded Fst toxin affects membrane permeability and alters cellular responses to lantibiotics. Journal of bacteriology 40 12644486
2002 Participation of the lateral septal nuclei (LSN) in the antidepressant-like actions of progesterone in the forced swimming test (FST). Behavioural brain research 39 12191804
2012 Localizing F(ST) outliers on a QTL map reveals evidence for large genomic regions of reduced gene exchange during speciation-with-gene-flow. Molecular ecology 38 23057835
2012 Differential introgression from a sister species explains high F(ST) outlier loci within a mussel species. Journal of evolutionary biology 36 23199184
2007 Increased sensitivity to antidepressants of D3 dopamine receptor-deficient mice in the forced swim test (FST). European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 36 17804207
1999 Minisatellite mutational processes reduce F(st) estimates. Human genetics 35 10647891
2008 Coalescence times and FST under a skewed offspring distribution among individuals in a population. Genetics 34 19047415
2008 F(ST) and Q(ST) under neutrality. Genetics 30 18780742
2010 Solution structure and membrane binding of the toxin fst of the par addiction module. Biochemistry 29 20677831
2014 Worldwide F(ST) estimates relative to five continental-scale populations. Annals of human genetics 27 26460400
2021 DNA fingerprinting, fixation-index (Fst), and admixture mapping of selected Bambara groundnut (Vigna subterranea [L.] Verdc.) accessions using ISSR markers system. Scientific reports 23 34267249
2017 Examination of Enterococcus faecalis Toxin-Antitoxin System Toxin Fst Function Utilizing a Pheromone-Inducible Expression Vector with Tight Repression and Broad Dynamic Range. Journal of bacteriology 23 28348028
1999 Among-locus variation in Fst: fish, allozymes and the Lewontin-Krakauer test revisited. Genetics 23 10353907
2012 Characterization of the effects of an rpoC mutation that confers resistance to the Fst peptide toxin-antitoxin system toxin. Journal of bacteriology 21 23104812
2012 Quantitative analysis of follistatin (FST) promoter methylation in peripheral blood of patients with polycystic ovary syndrome. Reproductive biomedicine online 21 23265961
2007 Extreme individual marker F(ST )values do not imply population-specific selection in humans: the NRG1 example. Human genetics 20 17457614
2017 Polymorphisms of FST gene and their association with wool quality traits in Chinese Merino sheep. PloS one 19 28384189
1977 Variation in allele frequencies among caste groups of the Dhangars of Maharashtra, India: an analysis with Wright's Fst statistic. Annals of human biology 18 900891
2019 , Jost's D, and FST are similarly constrained by allele frequencies: A mathematical, simulation, and empirical study. Molecular ecology 17 30589985
2020 Discovery of selection-driven genetic differences of Duroc, Landrace, and Yorkshire pig breeds by EigenGWAS and Fst analyses. Animal genetics 16 32400898
2020 Disagreement in FST estimators: A case study from sex chromosomes. Molecular ecology resources 16 32543001
2003 A study of Y-chromosome microsatellite variation in sub-Saharan Africa: a comparison between F(ST) and R(ST) genetic distances. Human biology 15 14527196
1973 Penetration into host cells of naked, partially injected (post-FST) DNA of bacteriophage T5. Journal of virology 15 4583885
2020 The Fst/Ldr Family of Type I TA System Toxins: Potential Roles in Stress Response, Metabolism and Pathogenesis. Toxins 14 32722354
2008 The joint effects of selection and dominance on the QST - FST contrast. Genetics 14 18984567
1982 Unique features of retrovirus expression in F/St mice. Journal of virology 14 6286989
2022 Mathematical constraints on F: multiallelic markers in arbitrarily many populations. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 13 35430885
1977 The use of the FST statistic of Wright for estimating the effects of genetic drift, selection and migration populations, with special reference to Ireland. Human heredity 13 863462
2022 Genome-Wide Association Study and FST Analysis Reveal Four Quantitative Trait Loci and Six Candidate Genes for Meat Color in Pigs. Frontiers in genetics 12 35464836
2004 The effect of unequal migration rates on FST. Theoretical population biology 9 15465120
2022 Covariance of pairwise differences on a multi-species coalescent tree and implications for FST. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 8 35430886
2022 Co-fermentation of non-Saccharomyces yeasts with Lactiplantibacillus plantarum FST 1.7 for the production of non-alcoholic beer. European food research and technology = Zeitschrift fur Lebensmittel-Untersuchung und -Forschung. A 8 36466321
2022 Identification of genes associated with feather color in Liancheng white duck using FST analysis. Animal genetics 7 35670225
1985 Feeding suppression induced by a fecal anorexigenic substance (FS-T). Physiology & behavior 7 3898164
2020 Expression and polymorphism of Follistatin (FST) gene and its association with growth traits in native and exotic chicken. Animal biotechnology 6 33170076
2018 FST between archaic and present-day samples. Heredity 6 30538303
2023 Follistatin (FST) is expressed in buffalo (Bubalus bubalis) ovarian follicles and promotes oocyte maturation and early embryonic development. Reproduction in domestic animals = Zuchthygiene 5 37917549
2019 The Relationship Between Haplotype-Based F and Haplotype Length. Genetics 5 31285255
2008 FABSIM: a software for generating FST distributions with various ascertainment biases. Bioinformatics (Oxford, England) 5 18845580
2024 FST and genetic diversity in an island model with background selection. PLoS genetics 4 39621755
2010 The distribution of Fst and other genetic statistics for a class of population structure models. Journal of mathematical biology 4 20186418
2023 A Novel c.100C > G Mutation in the FST Gene and Its Relation With the Reproductive Traits of Awassi Ewes. Bioinformatics and biology insights 3 37153841
2017 Estimation of FST and the Impact of de novo Mutation. Human heredity 3 28768256
2016 Expression, Regulation, and Functional Characterization of FST Gene in Porcine Granulosa Cells. Animal biotechnology 3 27565874
2012 Mutational analysis of the FST gene in Chinese women with idiopathic premature ovarian failure. Climacteric : the journal of the International Menopause Society 3 23113792
2025 Comparative Transcriptome Analysis Reveals the Role of the FST Gene in Goose Muscle Development. Animals : an open access journal from MDPI 2 41153936
2023 FST estimates of 94 populations in China based on STR markers. Forensic science international. Genetics 2 36893618
2023 Synthesis and antibacterial activity of FST and its effects on inflammatory response and intestinal barrier function in mice infected with Escherichia coli O78. International immunopharmacology 2 38109839
2018 BlockFeST: Bayesian calculation of region-specific FST to detect local adaptation. Bioinformatics (Oxford, England) 2 29718170
2015 Mapping genetic determinants of viral traits with FST and quantitative trait locus (QTL) approaches. Virology 2 26186573
2003 [Assessment of population differentiation using DNA fingerprinting and modified Wright's Fst-statistics]. Genetika 2 12669419
1999 FST, a female-specific transcript from the medfly Ceratitis capitata (Diptera: Tephritidae). Insect molecular biology 2 10634972
1998 [Selective structure of the gene pool. II. Standard method using F(ST) statistics]. Genetika 2 9879018
2025 FST Polymorphisms Associate with Musculoskeletal Traits and Modulate Exercise Response Differentially by Sex and Modality in Northern Han Chinese Adults. Genes 1 40725466
2025 Location and Identity of Photoreceptors Contributing to the Full-Field Stimulus Test (FST). Investigative ophthalmology & visual science 1 41147951
2009 Interlocus variance of F(ST) provides evidence for directional selection over an olfactory receptor gene in Coho salmon (Oncorhynchus kisutch) populations. Marine genomics 1 21798181
1998 [Interpopulation diversity of the gene pool: beta distribution of Wright's F(ST) statistics]. Genetika 1 9749343
2026 Integrated GWAS and Fst analysis identify flowering-time regulatory genes in maize. The plant genome 0 41565589

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