Analysis of DNA methylation changes following Cfp1 knockout in mouse spermatocytes

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.