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A Gata2-Dependent Transcription Network Regulates Uterine Progesterone Responsiveness and Endometrial Function.
- Source :
-
Cell reports [Cell Rep] 2016 Oct 25; Vol. 17 (5), pp. 1414-1425. - Publication Year :
- 2016
-
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.<br /> (Published by Elsevier Inc.)
- Subjects :
- Animals
Base Sequence
Conserved Sequence genetics
Embryo Implantation
Female
GATA2 Transcription Factor metabolism
Humans
Mice
Phosphoproteins metabolism
Pregnancy
Progesterone blood
Protein Binding genetics
Receptors, Progesterone metabolism
Signal Transduction genetics
Trans-Activators metabolism
Transcription Factors metabolism
Transcription, Genetic
Tumor Suppressor Proteins metabolism
Endometrium metabolism
Gene Regulatory Networks genetics
Progesterone metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 17
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 27783953
- Full Text :
- https://doi.org/10.1016/j.celrep.2016.09.093