title: A Gata2-Dependent Transcription Network Regulates Uterine Progesterone Responsiveness and Endometrial Function.
abstract: Altered progesterone responsiveness leads to female infertility and cancer, but underlying mechanisms remain unclear. Mice with uterine-specific ablation of GATA binding protein 2 (Gata2) are infertile, showing failures in embryo implantation, endometrial decidualization, and uninhibited estrogen signaling. Gata2 deficiency results in reduced progesterone receptor (PGR) expression and attenuated progesterone signaling, as evidenced by genome-wide expression profiling and chromatin immunoprecipitation. GATA2 not only occupies at and promotes expression of the Pgr gene but also regulates downstream progesterone responsive genes in conjunction with the PGR. Additionally, Gata2 knockout uteri exhibit abnormal luminal epithelia with ectopic TRP63 expressing squamous cells and a cancer-related molecular profile in a progesterone-independent manner. Lastly, we found a conserved GATA2-PGR regulatory network in both human and mice based on gene signature and path analyses using gene expression profiles of human endometrial tissues. In conclusion, uterine Gata2 regulates a key regulatory network of gene expression for progesterone signaling at the early pregnancy stage.
authors: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors: Cory A
authors: CA
authors: Rubel
authors: Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
authors: San-Pin
authors: SP
authors: Wu
authors: Department of Family Health Care Nursing, University of California at San Francisco, San Francisco, CA 94143, USA.
authors: Lin
authors: L
authors: Lin
authors: Division of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
authors: Tianyuan
authors: T
authors: Wang
authors: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors: Rainer B
authors: RB
authors: Lanz
authors: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors: Xilong
authors: X
authors: Li
authors: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors: Ramakrishna
authors: R
authors: Kommagani
authors: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors: Heather L
authors: HL
authors: Franco
authors: Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
authors: Sally A
authors: SA
authors: Camper
authors: Department of Pediatrics, Medicine, Molecular Physiology & Biophysics, Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors: Qiang
authors: Q
authors: Tong
authors: Department of Obstetrics and Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, MI 48824, USA.
authors: Jae-Wook
authors: JW
authors: Jeong
authors: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors: John P
authors: JP
authors: Lydon
authors: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Electronic address: francesco.demayo@nih.gov.
authors: Francesco J
authors: FJ
authors: DeMayo
mesh_terms: D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence / Q000235:genetics; D010064:Embryo Implantation; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D050989:GATA2 Transcription Factor / Q000378:metabolism; D053263:Gene Regulatory Networks / Q000235:genetics*; D006801:Humans; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism; D011247:Pregnancy; D011374:Progesterone / Q000097:blood / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D011980:Receptors, Progesterone / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D050989:GATA2 Transcription Factor; D010750:Phosphoproteins; D011980:Receptors, Progesterone; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C486419:Trp63 protein, mouse; D025521:Tumor Suppressor Proteins; D011374:Progesterone
keywords: GATA2; TRP63; endometrium; infertility; path analysis; pregnancy; progesterone; progesterone receptor; structural equation modeling; uterus