title: Epigenetic regulation of alternative promoters and enhancers in progenitor, immature, and mature gonadotrope cell lines.
abstract: Gonadotrope cell identity genes emerge in a stepwise process during mouse pituitary development. Cga, encoding for the α-subunit of TSH, LH, and FSH, is initially detected at E11.5 followed by Gnrhr and steroidogenic factor Sf1 at E13.5, specifying cells engaged in a gonadotrope cell fate. Lhb and Fshb appear at E16.5 and 17.5, respectively, typifying differentiated gonadotrope cells. Using the αT1-1, αT3-1 and LβT2 cell lines recapitulating these stages of gonadotrope differentiation, DNA methylation at Gnrhr and Sf1 was investigated. Regulatory regions were found hypermethylated in progenitor αT1-1 cells and hypomethylated in differentiated LβT2 cells. Abundance of RNA polymerase II together with active histone modifications including H3K4me1, H3K4me3, and H3K27ac were strictly correlated with DNA hypomethylation. Analyses of epigenomic modifications and chromatin accessibility were further extended to Isl1, Lhx3, Gata2, and Pitx2, highlighting alternative usages of specific regulatory gene domains in progenitor αT1-1, immature αT3-1, and mature LβT2 gonadotrope cells.
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, Biologie Fonctionnelle et Adaptative (BFA), F-75013, Paris, France; CNRS UMR 8251, F-75013, Paris, France; Physiologie de l'axe gonadotrope INSERM U1133, F-75013, Paris, France. Electronic address: jean-noel.laverriere@univ-paris-diderot.fr.
authors.forename: Jean-Noël
authors.initials: JN
authors.lastname: Laverrière
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, Biologie Fonctionnelle et Adaptative (BFA), F-75013, Paris, France; CNRS UMR 8251, F-75013, Paris, France; Physiologie de l'axe gonadotrope INSERM U1133, F-75013, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: L'Hôte
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, Biologie Fonctionnelle et Adaptative (BFA), F-75013, Paris, France; CNRS UMR 8251, F-75013, Paris, France; Physiologie de l'axe gonadotrope INSERM U1133, F-75013, Paris, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Tabouy
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, Biologie Fonctionnelle et Adaptative (BFA), F-75013, Paris, France; CNRS UMR 8251, F-75013, Paris, France; Physiologie de l'axe gonadotrope INSERM U1133, F-75013, Paris, France.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Schang
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, Biologie Fonctionnelle et Adaptative (BFA), F-75013, Paris, France; CNRS UMR 8251, F-75013, Paris, France; Physiologie de l'axe gonadotrope INSERM U1133, F-75013, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Quérat
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, Biologie Fonctionnelle et Adaptative (BFA), F-75013, Paris, France; CNRS UMR 8251, F-75013, Paris, France; Physiologie de l'axe gonadotrope INSERM U1133, F-75013, Paris, France.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Cohen-Tannoudji
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D019175:DNA Methylation; D004742:Enhancer Elements, Genetic; D044127:Epigenesis, Genetic; D057890:Epigenomics / Q000379:methods; D018507:Gene Expression Regulation, Developmental; D015292:Glycoprotein Hormones, alpha Subunit / Q000235:genetics; D052681:Gonadotrophs / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D011401:Promoter Regions, Genetic; D000072260:RNA Splicing Factors / Q000235:genetics; D011966:Receptors, LHRH / Q000235:genetics
chemical_list: D015292:Glycoprotein Hormones, alpha Subunit; D000072260:RNA Splicing Factors; D011966:Receptors, LHRH; C491514:Sf1 protein, mouse
keywords: DNA methylation; GATA binding proteins; GnRH receptor; Gonadotrope cell lines; Gonadotrope differentiation; Histones modifications; LIM-Homeodomain proteins; Steroidogenic factor 1