KLF15 negatively regulates estrogen-induced epithelial cell proliferation by inhibition of DNA replication licensing.

ABSTRACT: In the epithelial compartment of the uterus, estradiol-17β (E(2)) induces cell proliferation while progesterone (P(4)) inhibits this response and causes differentiation of the cells. In this study, we identified the mechanism whereby E(2) and P(4) reciprocally regulate the expression of minichromosome maintenance (MCM)-2, a protein that is an essential component of the hexameric MCM-2 to 7 complex required for DNA synthesis initiation. We show in the uterine epithelium that Kruppel-like transcription (KLF) factors, KLF 4 and 15, are inversely expressed; most importantly, they bind to the Mcm2 promoter under the regulation of E(2) and P(4)E(2), respectively. After P(4)E(2) exposure and in contrast to E(2) treated mice, the Mcm2 promoter displays increased histone 3 (H3) methylation and the

SUBMITTER: Ray S 

PROVIDER: S-EPMC3361390 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature