Analysis of DNA methylation changes following Cfp1 knockout in mouse spermatocytes.

Abstract

Objective: 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.

Methods: We performed genome-wide methylation analysis using reduced-representation bisulfite sequencing (RRBS) on spermatocytes isolated from Cfp1 knockout (KO) and wild-type (WT) mice. Promoter methylation changes were integrated with publicly available microarray and ChIP-seq data to identify genes regulated by CFP1.

Results: 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.

Conclusion: 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.