Park Chanhyeok, Choi Youngsok, Yoo Seonho, La Hyeonwoo, Hong Kwonho
Department of Stem Cell and Regenerative Biotechnology, Institute of Advanced Regenerative Science, Konkuk University, Seoul, Korea.
Anim Biosci. 2025 Aug;38(8):1570-1579. doi: 10.5713/ab.24.0807. Epub 2025 Feb 27.
Spermatogenesis is a complex biological process that encompasses meiosis in spermatocytes and the dynamic epigenetic alterations that ensure the inheritance of genetic traits. CXXC finger protein 1 (CFP1, Cfp1, CXXC1, Cxxc1) is a critical component of the SET domain-containing 1A histone lysine methyltransferase complex that catalyzes histone H3K4 methylation and has a specific binding domain for unmethylated CpG DNA. However, our current understanding of CFP1's role in the genome-wide regulation of DNA and H3K4 methylation remains limited.
We performed genome-wide methylation analysis using reduced-representation bisulfite sequencing on spermatocytes isolated from Cfp1 knockout and wild-type mice. Promoter methylation changes were integrated with publicly available microarray and ChIP-seq data to identify genes regulated by CFP1.
CFP1 depletion led to significant alterations in DNA methylation, particularly in promoter regions of genes associated with meiosis, transcription regulation, and chromatin remodeling. A total of 21 genes were identified as direct targets of CFP1, exhibiting reduced promoter methylation and CFP1 binding.
Our study findings contribute to elucidating the regulatory mechanisms of CFP1 in spermatocytes, providing valuable insights into the reproductive process and advancing our understanding of the underlying causes of infertility.
精子发生是一个复杂的生物学过程,包括精母细胞中的减数分裂以及确保遗传性状遗传的动态表观遗传改变。CXXC 指蛋白 1(CFP1、Cfp1、CXXC1、Cxxc1)是含 SET 结构域的 1A 组蛋白赖氨酸甲基转移酶复合物的关键组成部分,该复合物催化组蛋白 H3K4 甲基化,并且对未甲基化的 CpG DNA 具有特异性结合结构域。然而,我们目前对 CFP1 在全基因组范围内对 DNA 和 H3K4 甲基化调控作用的理解仍然有限。
我们使用简化代表性亚硫酸氢盐测序对从 Cfp1 基因敲除小鼠和野生型小鼠分离的精母细胞进行全基因组甲基化分析。将启动子甲基化变化与公开可用的微阵列和 ChIP-seq 数据整合,以鉴定受 CFP1 调控的基因。
CFP1 缺失导致 DNA 甲基化发生显著改变,特别是在与减数分裂、转录调控和染色质重塑相关基因的启动子区域。总共鉴定出 21 个基因作为 CFP1 的直接靶标,这些基因的启动子甲基化减少且有 CFP1 结合。
我们的研究结果有助于阐明 CFP1 在精母细胞中的调控机制,为生殖过程提供有价值的见解,并加深我们对不孕症潜在原因的理解。