한빛사논문
- 조회862
Seung Chel Yang 1,10, Mira Park 1,10, Kwon-Ho Hong 2, Hyeonwoo La 2, Chanhyeok Park 2, Peike Wang 3, Gaizhen Li 3, Qionghua Chen 3, Youngsok Choi 2, Francesco J. DeMayo 4, John P. Lydon 5, David G. Skalnik 6, Hyunjung J. Lim 7, Seok-Ho Hong 8,9, So Hee Park 1, Yeon Sun Kim 1, Hye-Ryun Kim 1 & Haengseok Song 1,*
1Department of Biomedical Science, CHA University, Seongnam, Gyeonggi 13488, Korea.
2Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Korea.
3Fujian Provincial Key Laboratory of Reproductive Health Research, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China.
4Department of Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 12233, USA.
5Department of Molecular and Cellular Biology and Center for Reproductive Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
6Department of Biology, School of Science, Indiana UniversityPurdue University Indianapolis, Indianapolis, IN 46202, USA.
7Department of Veterinary Science, Konkuk University, Seoul 05029, Korea.
8Department of Internal Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do 24431, Korea.
9KW-Bio Co., Ltd, Wonju 26493, Korea.
10These authors contributed equally: Seung Chel Yang, Mira Park.
*Corresponding author: correspondence to Haengseok Song
Abstract
Progesterone (P4) is required for the preparation of the endometrium for a successful pregnancy. P4 resistance is a leading cause of the pathogenesis of endometrial disorders like endometriosis, often leading to infertility; however, the underlying epigenetic cause remains unclear. Here we demonstrate that CFP1, a regulator of H3K4me3, is required for maintaining epigenetic landscapes of P4-progesterone receptor (PGR) signaling networks in the mouse uterus. Cfp1f/f;Pgr-Cre (Cfp1d/d) mice showed impaired P4 responses, leading to complete failure of embryo implantation. mRNA and chromatin immunoprecipitation sequencing analyses showed that CFP1 regulates uterine mRNA profiles not only in H3K4me3-dependent but also in H3K4me3-independent manners. CFP1 directly regulates important P4 response genes, including Gata2, Sox17, and Ihh, which activate smoothened signaling pathway in the uterus. In a mouse model of endometriosis, Cfp1d/d ectopic lesions showed P4 resistance, which was rescued by a smoothened agonist. In human endometriosis, CFP1 was significantly downregulated, and expression levels between CFP1 and these P4 targets are positively related regardless of PGR levels. In brief, our study provides that CFP1 intervenes in the P4-epigenome-transcriptome networks for uterine receptivity for embryo implantation and the pathogenesis of endometriosis.
논문정보
- Research article
- 2023년 06월 (BRIC 등록일 2023-06-08)
- 국내(교신)+국외 연구진
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