Table 2 DMRs relevance in CTR-CZ differentially expressed genes
Gene | DMR location | DMR relevance | Methylation change | Expression change | Gene relevance | |
|---|---|---|---|---|---|---|
BBS5 | Intron | Enhancer? | Hypermethylated | Downregulated in early spermatids | Necessary for the generation of both cilia and flagella [41] | |
C2orf92 | Promoter, exon, intron, LMR | Promoter | Hypermethylated | Downregulated in later stages of spermatogenesis | Enriched in the testis [42] | |
C10orf120 | Promoter, intron, UMR | Promoter | Hypermethylated | Downregulated in late spermatids | Enriched in the testis [42] | |
CFAP299 | Intron, LMR | Enhancer? | Hypermethylated | Downregulated in spermatogenesis | Encodes a cilia- and flagella associated protein recently shown to be involved in mice spermatogenesis [43] | |
DHX16 | GeneHancer element, exon, intron | Enhancer | Hypermethylated | Downregulated in later stages of spermatogenesis | Involved in mRNA splicing [44] | |
MCTP1 | Intron, LMR | Enhancer? | Hypermethylated | Downregulated in later stages of spermatogenesis | Exclusively found in sperm samples with which pregnancy was achieved [45] | |
PACRG | Intron | Enhancer? | Hypermethylated | Downregulated from pachytene spermatocytes onwards | Role in sperm differentiation and its deletion causes male infertility in mice [46] | |
PLAC8L1 | Intron | Enhancer? | Hypermethylated | Downregulated in late spermatids | Understudied gene enriched in the testis [42] | |
PPP3CC | Promoter, intron | Promoter | Hypermethylated | Upregulated in leptotene and diplotene stages | Testis-specific calcineurin isoform that confers midpiece flexibility during the sperm epididymal transit; ablation causes male infertility in mice [47] | |
PPP1R36 | Promoter, GeneHancer element, UMR | Promoter | Hypermethylated | Downregulated in zygotene and pachytene spermatocytes, meiotic divisions and early spermatids | Inhibits phosphatase activity of PP1 complexes and has been implicated in enhancing autophagy during spermatogenesis [48] | |
SPAG16 | Intron, UMR | Enhancer? | Hypermethylated | Downregulated in later stages of spermatogenesis | Detected in the sperm flagellum axoneme and necessary for its function [49] | |
TCP10L2 | Intron | Enhancer? | Hypomethylated | Downregulated in later stages of spermatogenesis | Enriched in the epididymis and testis [42] | |
ZFAND4 | Intron | Enhancer? | Hypermethylated | Upregulation in diplotene and meiotic divisions | Enriched in the testis [42] | |