ArticleProceedings of the National Academy of Sciences of the United States of America2012
KLF15 negatively regulates estrogen-induced epithelial cell proliferation by inhibition of DNA replication licensing.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 88 citations in OpenAlex.
- Postnatal maternal care impacts hypothalamicbioRxiv : the preprint server for biology · 2025Article
- Uterine cyclin A2-deficient mice as a model of female early pregnancy loss.The Journal of clinical investigation · 2024Article
- Loss of KLF15 impairs endometrial receptivity by inhibiting EMT in endometriosis.The Journal of endocrinology · 2024Article
- The genetic regulatory architecture and epigenomic basis for age-related changes in rattlesnake venom.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A GREB1-steroid receptor feedforward mechanism governs differential GREB1 action in endometrial function and endometriosis.Nature communications · 2024Article
- A common allele increases endometrial Wnt4 expression, with antagonistic implications for pregnancy, reproductive cancers, and endometriosis.Nature communications · 2024Article
- DCAF2 is essential for the development of uterine epithelia and mouse fertility.Frontiers in cell and developmental biology · 2024Article
- Molecular mechanism of aberrant decidualization in adenomyosis leading to reduced endometrial receptivity.Frontiers in endocrinology · 2024Review
- Krüppel-like factor 15 in liver diseases: Insights into metabolic reprogramming.Frontiers in pharmacology · 2023Review
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- Loss of MIG-6 results in endometrial progesterone resistance via ERBB2.Nature communications · 2022Article
- The functions and prognostic value of Krüppel-like factors in breast cancer.Cancer cell international · 2022Article
- Shp2 in uterine stromal cells critically regulates on time embryo implantation and stromal decidualization by multiple pathways during early pregnancy.PLoS genetics · 2022Article
- MiR-181a promotes cell proliferation and migration through targeting KLF15 in papillary thyroid cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Article
- Expression and Prognosis Value of the KLF Family Members in Colorectal Cancer.Journal of oncology · 2022Article
- Depletion of Kruppel-like factor 15 sensitized gliomas to temozolomide cytotoxicity throughBiochemistry and biophysics reports · 2021Article
- Endometrial receptivity and implantation require uterine BMP signaling through an ACVR2A-SMAD1/SMAD5 axis.Nature communications · 2021Article
- Sex-biased genes and metabolites explain morphologically sexual dimorphism and reproductive costs in Salix paraplesia catkins.Horticulture research · 2021Article
- EWS-FLI1 regulates and cooperates with core regulatory circuitry in Ewing sarcoma.Nucleic acids research · 2020Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
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 recruitment of histone deacetylase 1 and 3 with the concomitant deacetylation of H3. This increased methylation and decreased acetylation is associated with an inhibition of RNA polymerase II binding, indicating an inactive Mcm2 promoter following P(4)E(2) treatment. Using transient transfection assays in the Ishikawa endometrial cell line, we demonstrate that Mcm2 promoter activity is hormonally stimulated by E(2) and that KLF15 inhibits this E(2) enhanced transcription. KLF15 expression also blocks Ishikawa cell proliferation through inhibition of MCM2 protein level. Importantly, in vivo expression of KLF15 in an estrogenized uterus mimics P(4)'s action by inhibiting E(2)-induced uterine epithelial MCM-2 expression and DNA synthesis. KLF15 is therefore a downstream physiological mediator of progesterone's cell cycle inhibitory action in the uterine epithelium.
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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.