Abstract
In mammals, DNA methylation is restricted to cytosines of CpG dinucleotides, which are frequently found in short genomic regions including gene promoters. Methylation within CpG-rich regions around promoters tends to repress gene expression; thus, the CpG islands of housekeeping genes are normally unmethylated. We previously described a testis-specific single-exon gene containing a CpG-rich sequence that is methylated and thus repressed in somatic cells, whereas its expression in spermatogenic cells requires that it be hypomethylated. However, the relationship among the specific expression of spermatogenic genes, their methylation dynamics, and their CpG frequencies are poorly understood. Here, we analyzed the methylation patterns of the sphort genomic region around the transcription start site in spermatogenic cell-specific single-exon genes of various CpG contents. By using UniGene and Ensembl database analyses of the mouse genome and reverse transcription-PCR, we identified 39 single-exon genes that are exclusively expressed in spermatogeniccells. Regardless of their specific expression characteristics, genes containing higher (7 to 14 CpGs in 200 bp; mean = 12) and lower (2 to 6 CpGs in 200 bp; mean = 3.1) number ofCpG were hypo- and hyper-methylated, respectively, in all cell types examined, including spermatogeniccells. We found that genes with intermediate number of CpG (2 to 11 CpGs in 200 bp; mean = 6.9) are methylated in somatic cells, but not in male germ cells. These results suggest that DNA methylation dynamics of spermatogenic cell-specific single-exon genes are associated with CpG content, and the methylation status are stably maintained throughout male germ cell development.
Highlights
In mammals, DNA methylation occurs at cytosine residues in CpG dinucleotides and is heritable during cell division
Testis-specific expression of these genes is usually regulated by relatively short sequences in the gene promoter [18,19,20]. In addition to this type of regulatory mechanism involving the binding of transcription factors to cis-elements, we previously suggested that another type of mechanism, involving DNA methylation-induced gene suppression, might play a crucial role in gene expression during spermatogenesis
We identified all of the single-exon genes that are expressed exclusively inspermatogenic cells and examined their methylation profiles around the promoter to explore the methylation dynamics of testis-specific genes during spermatogenesis
Summary
DNA methylation occurs at cytosine residues in CpG dinucleotides and is heritable during cell division. CpG cytosine methylation is an epigenetic marker that is essential for normal embryonic development [1] This epigenetic modification of DNA is catalyzed by three DNA methyltransferases (Dnmts); Dnmt3a and Dnmt3b initiate de novo methylation and thereby establish new methylation patterns [2], and Dnmt is primarily involved in maintaining the methylation pattern [3]. Another member of the Dnmt family, Dnmt3L, lacks the Dnmt catalytic domain and is expressed during gametogenesis in the stages during which genomic imprints are established [4,5]. Male mice lacking Dnmt3L are infertile because they lack mature germ cells [4,5]
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