한빛사논문
- 조회860
Byeong Seong Ki # 1, Sung Han Shim # 1, Chanhyeok Park # 2, Hyunjin Yoo # 2, Hyeonwoo La 2, Ok-Hee Lee 1, Youngjoo Kwon 3, David G Skalnik 4, Yuki Okada 5, Ho-Geun Yoon 6, Jin-Hoi Kim 2, Kwonho Hong 7, Youngsok Choi 8
1Department of Biomedical Science, CHA University, Gyeonggi-do, 13488, Republic of Korea.
2Department of Stem Cell and Regenerative Biotechnology, Humanized Pig Center, Konkuk University, Seoul, 05029, Republic of Korea.
3College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, 03760, Republic of Korea.
4Department of Biology, School of Science, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202, USA.
5Institute for Quantitative Biosciences, The University of Tokyo, Bunkyo, Tokyo, 113-0032, Japan.
6Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
7Department of Stem Cell and Regenerative Biotechnology, Humanized Pig Center, Konkuk University, Seoul, 05029, Republic of Korea.
8Department of Stem Cell and Regenerative Biotechnology, Humanized Pig Center, Konkuk University, Seoul, 05029, Republic of Korea.
#Contributed equally.
These authors contributed equally: Byeong Seong Ki, Sung Han Shim, Chanhyeok Park, Hyunjin Yoo.
Corresponding authors: Correspondence to Kwonho Hong or Youngsok Choi.
Abstract
Meiosis occurs specifically in germ cells to produce sperm and oocytes that are competent for sexual reproduction. Multiple factors are required for successful meiotic entry, progression, and termination. Among them, trimethylation of histone H3 on lysine 4 (H3K4me3), a mark of active transcription, has been implicated in spermatogenesis by forming double-strand breaks (DSBs). However, the role of H3K4me in transcriptional regulation during meiosis remains poorly understood. Here, we reveal that mouse CXXC finger protein 1 (Cfp1), a component of the H3K4 methyltransferase Setd1a/b, is dynamically expressed in differentiating male germ cells and safeguards meiosis by controlling gene expression. Genetic ablation of mouse CFP1 in male germ cells caused complete infertility with failure in prophase I of the 1st meiosis. Mechanistically, CFP1 binds to genes essential for spermatogenesis, and its loss leads to a reduction in H3K4me3 levels and gene expression. Importantly, CFP1 is highly enriched within the promoter/TSS of target genes to elevate H3K4me3 levels and gene expression at the pachytene stage of meiotic prophase I. The most enriched genes were associated with meiosis and homologous recombination during the differentiation of spermatocytes to round spermatids. Therefore, our study establishes a mechanistic link between CFP1-mediated transcriptional control and meiotic progression and might provide an unprecedented genetic basis for understanding human sterility.
논문정보
- Research article
- 2022년 08월 (BRIC 등록일 2022-10-14)
- 국내(교신)+국외 연구진
- 생명과학 > 노화/암생물학
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