title: A murine uterine transcriptome, responsive to steroid receptor coactivator-2, reveals transcription factor 23 as essential for decidualization of human endometrial stromal cells.
abstract: Recent data from human and mouse studies strongly support an indispensable role for steroid receptor coactivator-2 (SRC-2)-a member of the p160/SRC family of coregulators-in progesterone-dependent endometrial stromal cell decidualization, an essential cellular transformation process that regulates invasion of the developing embryo into the maternal compartment. To identify the key progesterone-induced transcriptional changes that are dependent on SRC-2 and required for endometrial decidualization, we performed comparative genome-wide transcriptional profiling of endometrial tissue RNA from ovariectomized SRC-2(flox/flox) (SRC-2(f/f) [control]) and PR(cre/+)/SRC-2(flox/flox) (SRC-2(d/d) [SRC-2-depleted]) mice, acutely treated with vehicle or progesterone. Although data mining revealed that only a small subset of the total progesterone-dependent transcriptional changes is dependent on SRC-2 (∼13%), key genes previously reported to mediate progesterone-driven endometrial stromal cell decidualization are present within this subset. Along with providing a more detailed molecular portrait of the decidual transcriptional program governed by SRC-2, the degree of functional diversity of these progesterone mediators underscores the pleiotropic regulatory role of SRC-2 in this tissue. To showcase the utility of this powerful informational resource to uncover novel signaling paradigms, we stratified the total SRC-2-dependent subset of progesterone-induced transcriptional changes in terms of novel gene expression and identified transcription factor 23 (Tcf23), a basic-helix-loop-helix transcription factor, as a new progesterone-induced target gene that requires SRC-2 for full induction. Importantly, using primary human endometrial stromal cells in culture, we demonstrate that TCF23 function is essential for progesterone-dependent decidualization, providing crucial translational support for this transcription factor as a new decidual mediator of progesterone action.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas.
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Kommagani
authors.forename: Maria M
authors.initials: MM
authors.lastname: Szwarc
authors.forename: Ertug
authors.initials: E
authors.lastname: Kovanci
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Creighton
authors.forename: Bert W
authors.initials: BW
authors.lastname: O'Malley
authors.forename: Francesco J
authors.initials: FJ
authors.lastname: Demayo
authors.forename: John P
authors.initials: JP
authors.lastname: Lydon
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D003656:Decidua / Q000166:cytology* / Q000502:physiology; D005260:Female; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D051958:Nuclear Receptor Coactivator 2 / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D011374:Progesterone / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D017154:Stromal Cells / Q000166:cytology* / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology; D059467:Transcriptome / Q000502:physiology; D014599:Uterus / Q000166:cytology / Q000502:physiology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051958:Nuclear Receptor Coactivator 2; D011374:Progesterone; D034741:RNA, Small Interfering; C498001:NCOA2 protein, human; C498002:Ncoa2 protein, mouse; C485762:TCF23 protein, human; C404514:Tcf23 protein, mouse
keywords: decidualization; endometrium; human; microarray; mouse; progesterone; steroid receptor coactivator-2; transcription factor 23