title: Progesterone receptor transcriptome and cistrome in decidualized human endometrial stromal cells.
abstract: Decidualization is a complex process involving cellular proliferation and differentiation of the endometrial stroma that is required to establish and support pregnancy. Progesterone acting via its nuclear receptor, the progesterone receptor (PGR), is a critical regulator of decidualization and is known to interact with certain members of the activator protein-1 (AP-1) family in the regulation of transcription. In this study, we identified the cistrome and transcriptome of PGR and identified the AP-1 factors FOSL2 and JUN to be regulated by PGR and important in the decidualization process. Direct targets of PGR were identified by integrating gene expression data from RNA sequencing with the whole-genome binding profile of PGR determined by chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) in primary human endometrial stromal cells exposed to 17β-estradiol, medroxyprogesterone acetate, and cAMP to promote in vitro decidualization. Ablation of FOSL2 and JUN attenuates the induction of 2 decidual marker genes, IGFBP1 and PRL. ChIP-seq analysis of genomic binding revealed that FOSL2 is bound in proximity to 8586 distinct genes, including nearly 80% of genes bound by PGR. A comprehensive assessment of the PGR-dependent decidual transcriptome integrated with the genomic binding of PGR identified FOSL2 as a potentially important transcriptional coregulator of PGR via direct interaction with regulatory regions of genes actively regulated during decidualization.
authors.affiliation: Division of Reproductive Endocrinology and Infertility (E.C.M., E.K., W.E.G.), Department of Obstetrics and Gynecology, Texas Children's Hospital Pavilion for Women, Department of Molecular and Cellular Biology (Y.M.V., X.L., R.K., R.B.L., F.J.D.), and Department of Molecular and Human Genetics (L.J., R.C.), Baylor College of Medicine, Houston, Texas 77030.
authors.forename: Erik C
authors.initials: EC
authors.lastname: Mazur
authors.forename: Yasmin M
authors.initials: YM
authors.lastname: Vasquez
authors.forename: Xilong
authors.initials: X
authors.lastname: Li
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Kommagani
authors.forename: Lichun
authors.initials: L
authors.lastname: Jiang
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.forename: Rainer B
authors.initials: RB
authors.lastname: Lanz
authors.forename: Ertug
authors.initials: E
authors.lastname: Kovanci
authors.forename: William E
authors.initials: WE
authors.lastname: Gibbons
authors.forename: Francesco J
authors.initials: FJ
authors.lastname: DeMayo
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D004717:Endometrium / Q000166:cytology*; D005260:Female; D051921:Fos-Related Antigen-2 / Q000378:metabolism; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics* / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics
chemical_list: C497872:FOSL2 protein, human; D051921:Fos-Related Antigen-2; C032231:IGFBP1 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1; D011980:Receptors, Progesterone; D018808:Transcription Factor AP-1