Multimodal regulation of E2F1 gene expression by progestins.

Molecular and Cellular Biology
Hilary E WadeDonald P McDonnell

Abstract

An analysis of mRNA expression in T47D breast cancer cells treated with the synthetic progestin R5020 revealed a subset of progesterone receptor (PR) target genes that are enriched for E2F binding sites. Following up on this observation, we determined that PR-B acts in both direct and indirect manners to positively upregulate E2F1 expression in T47D cells. The direct effects of PR on E2F1 expression were confirmed by chromatin immunoprecipitation (ChIP) analysis, which indicated that the agonist-bound receptor was recruited to several enhancer elements proximal to the E2F1 transcript. However, we also noted that cycloheximide partially inhibits R5020 induction of E2F1 expression, indicating that the ligand-dependent actions of PR on this gene may involve additional indirect regulatory pathways. In support of this hypothesis, we demonstrated that treatment with R5020 significantly increases both hyperphosphorylation of Rb and recruitment of E2F1 to its own promoter, thus activating a positive feedback loop that further amplifies its transcription. Furthermore, we established that PR-mediated induction of Krüppel-like factor 15 (KLF15), which can bind to GC-rich DNA within the E2F1 promoter, is required for maximal induction of E...Continue Reading

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Citations

Oct 13, 2011·DNA and Cell Biology·Xiao ZhaoYaosheng Chen
Sep 22, 2010·Molecular and Cellular Biology·Alexey S RevenkoHong-Wu Chen
Oct 29, 2010·Molecular Endocrinology·Sakiko KobayashiDonald P McDonnell
Dec 25, 2012·Drug Discovery Today. Therapeutic Strategies·Darlene K Taylor, Phyllis C Leppert
Mar 20, 2014·General and Comparative Endocrinology·Joseph R Knoedler, Robert J Denver
Mar 4, 2014·Developmental Biology·Paritosh PrasharAmitabha Bandyopadhyay
May 7, 2013·General and Comparative Endocrinology·Qingqing WeiYunliang Jiang
Nov 26, 2011·The Biochemical Journal·Laura NovellasdemuntRamon Bartrons
Apr 15, 2015·Cellular Oncology (Dordrecht)·Tomomi YodaHironobu Sasano
Feb 20, 2014·Proceedings of the National Academy of Sciences of the United States of America·Elizabeth L ScholtzAlan J Conley
Mar 23, 2011·Reproductive Sciences·Hilary RoederPhyllis C Leppert
Jan 2, 2016·Proceedings of the National Academy of Sciences of the United States of America·Diana MonsivaisMartin M Matzuk

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