title: COUP-TFII regulates human endometrial stromal genes involved in inflammation.
abstract: Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII; NR2F2) is an orphan nuclear receptor involved in cell-fate specification, organogenesis, angiogenesis, and metabolism. Ablation of COUP-TFII in the mouse uterus causes infertility due to defects in embryo attachment and impaired uterine stromal cell decidualization. Although the function of COUP-TFII in uterine decidualization has been described in mice, its role in the human uterus remains unknown. We observed that, as in mice, COUP-TFII is robustly expressed in the endometrial stroma of healthy women, and its expression is reduced in the ectopic lesions of women with endometriosis. To interrogate the role of COUP-TFII in human endometrial function, we used a small interfering RNA-mediated loss of function approach in primary human endometrial stromal cells. Attenuation of COUP-TFII expression did not completely block decidualization; rather it had a selective effect on gene expression. To better elucidate the role of COUP-TFII in endometrial stroma cell biology, the COUP-TFII transcriptome was defined by pairing microarray comparison with chromatin immunoprecipitation followed by deep sequencing. Gene ontology analysis demonstrates that COUP-TFII regulates a subset of genes in endometrial stroma cell decidualization such as those involved in cell adhesion, angiogenesis, and inflammation. Importantly this analysis shows that COUP-TFII plays a role in controlling the expression of inflammatory cytokines. The determination that COUP-TFII plays a role in inflammation may add insight into the role of COUP-TFII in embryo implantation and in endometrial diseases such as endometriosis.
authors.affiliation: Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. fdemayo@bcm.edu.
authors.forename: Xilong
authors.initials: X
authors.lastname: Li
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Large
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Creighton
authors.forename: Rainer B
authors.initials: RB
authors.lastname: Lanz
authors.forename: Jae-Wook
authors.initials: JW
authors.lastname: Jeong
authors.forename: Steven L
authors.initials: SL
authors.lastname: Young
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Lessey
authors.forename: Wilder A
authors.initials: WA
authors.lastname: Palomino
authors.forename: Sophia Y
authors.initials: SY
authors.lastname: Tsai
authors.forename: Francesco J
authors.initials: FJ
authors.lastname: Demayo
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001665:Binding Sites; D051837:COUP Transcription Factor II / Q000378:metabolism*; D002828:Choristoma / Q000235:genetics / Q000473:pathology; D047369:Chromatin Immunoprecipitation; D003656:Decidua / Q000378:metabolism; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000378:metabolism; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000235:genetics; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D051837:COUP Transcription Factor II; D034741:RNA, Small Interfering