ArticleMolecular endocrinology (Baltimore, Md.)2009
A composite intronic element directs dynamic binding of the progesterone receptor and GATA-2.
Article in Molecular endocrinology (Baltimore, Md.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 38 citations in OpenAlex.
- ViableFrontiers in immunology · 2026Article
- Review
- Progesterone Receptor-Mediated Regulation of Cellular Glucose andJournal of the Endocrine Society · 2022Article
- Illuminating the "Black Box" of Progesterone-Dependent Embryo Implantation Using Engineered Mice.Frontiers in cell and developmental biology · 2021Review
- Onapristone Extended Release: Safety Evaluation from Phase I-II Studies with an Emphasis on Hepatotoxicity.Drug safety · 2020Article
- Bioinformatics Analyses Determined the Distinct CNS and Peripheral Surrogate Biomarker Candidates Between Two Mouse Models for Progressive Multiple Sclerosis.Frontiers in immunology · 2019Article
- Oocyte cryopreservation for women with GATA2 deficiency.Journal of assisted reproduction and genetics · 2018Article
- Gene expression profiling of upregulated mRNAs in granulosa cells of bovine ovulatory follicles following stimulation with hCG.Reproductive biology and endocrinology : RB&E · 2017Article
- A Gata2-Dependent Transcription Network Regulates Uterine Progesterone Responsiveness and Endometrial Function.Cell reports · 2016Article
- Article
- Differential Regulation of Progesterone Receptor-Mediated Transcription by CDK2 and DNA-PK.Molecular endocrinology (Baltimore, Md.) · 2016Article
- Article
- WDR5 Expression Is Prognostic of Breast Cancer Outcome.PloS one · 2015Article
- Cyclin A2 and its associated kinase activity are required for optimal induction of progesterone receptor target genes in breast cancer cells.The Journal of steroid biochemistry and molecular biology · 2014Article
- EDD enhances cell survival and cisplatin resistance and is a therapeutic target for epithelial ovarian cancer.Carcinogenesis · 2014Article
- Lysine methylation of progesterone receptor at activation function 1 regulates both ligand-independent activity and ligand sensitivity of the receptor.The Journal of biological chemistry · 2014Article
- Acetylation at lysine 183 of progesterone receptor by p300 accelerates DNA binding kinetics and transactivation of direct target genes.The Journal of biological chemistry · 2014Article
- Deep sequencing reveals new aspects of progesterone receptor signaling in breast cancer cells.PloS one · 2014Article
- Control of endothelin-a receptor expression by progesterone is enhanced by synergy with Gata2.Molecular endocrinology (Baltimore, Md.) · 2013Article
- Novel roles for KLF1 in erythropoiesis revealed by mRNA-seq.Genome research · 2012Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The progesterone receptor (PR) plays a pivotal role in proper development and function of the mammary gland and has also been implicated in mammary tumorigenesis. PR is a ligand-activated transcription factor; however, relatively, little is known about its mechanisms of action at endogenous target promoters. The aim of our study was to identify a natural PR-responsive gene and investigate its transcriptional regulation in the mammary microenvironment. Our experiments revealed FKBP5 as a direct target of the PR, because it exhibited a rapid activation by progestin that was cycloheximide independent and correlated with recruitment of RNA polymerase II to the promoter. Site-directed mutagenesis and chromatin immunoprecipitation assays showed that progestin responsiveness is mediated through a composite element in the first intron, to which the PR binds concomitantly with GATA-2. Mutational analysis of the element revealed that the GATA-2 site is essential for progestin activation. Direct binding of PR to DNA contributes to the efficiency of activation but is not sufficient, suggesting that the receptor makes important protein-protein interactions as part of its mechanism of action at the FKBP5 promoter. Using chromatin immunoprecipitation assays we also determined that the intronic region is in communication with the promoter, probably via DNA looping. Time course analysis revealed a cyclical pattern of PR recruitment to the FKBP5 gene but a persistent recruitment to the mouse mammary tumor virus promoter, indicating that receptor cycling is a gene-specific phenomenon rather than a characteristic of the receptor itself. Our study offers new insight in the nature of PR-regulated transcription in mammary cancer cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.