title: The transcription factor FOXL2 mobilizes estrogen signaling to maintain the identity of ovarian granulosa cells.
abstract: FOXL2 is a lineage determining transcription factor in the ovary, but its direct targets and modes of action are not fully characterized. In this study, we explore the targets of FOXL2 and five nuclear receptors in murine primary follicular cells. We found that FOXL2 is required for normal gene regulation by steroid receptors, and we show that estrogen receptor beta (ESR2) is the main vector of estradiol signaling in these cells. Moreover, we found that FOXL2 directly modulates Esr2 expression through a newly identified intronic element. Interestingly, we found that FOXL2 repressed the testis-determining gene Sox9 both independently of estrogen signaling and through the activation of ESR2 expression. Altogether, we show that FOXL2 mobilizes estrogen signaling to establish a coherent feed-forward loop repressing Sox9. This sheds a new light on the role of FOXL2 in ovarian maintenance and function.
authors.affiliation: Institut Jacques Monod, Paris, France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Georges
authors.affiliation: Institut Jacques Monod, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: L'Hôte
authors.affiliation: Institut Jacques Monod, Paris, France.
authors.forename: Anne Laure
authors.initials: AL
authors.lastname: Todeschini
authors.affiliation: Institut Jacques Monod, Paris, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Auguste
authors.affiliation: Institut Jacques Monod, Paris, France.
authors.forename: Bérangère
authors.initials: B
authors.lastname: Legois
authors.affiliation: Institut Jacques Monod, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Zider
authors.affiliation: Institut Jacques Monod, Paris, France.
authors.forename: Reiner A
authors.initials: RA
authors.lastname: Veitia
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects; D016678:Genome; D006107:Granulosa Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics
chemical_list: D047629:Estrogen Receptor beta; D004967:Estrogens; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; C498893:Foxl2 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear; D004958:Estradiol
keywords: FOXL2; cell identity; chromosomes; estrogen; estrogen receptor; genes; human; mouse; ovary; transcription factor