Methylation of the Sox9 and Oct4 promoters and its correlation with gene expression during testicular development in the laboratory mouse

Abstract

Sox9 and Oct4 are two important regulatory factors involved in mammalian development. Sox9, a member of the group E Sox transcription factor family, has a crucial role in the development of the genitourinary system, while Oct4, commonly known as octamer binding transcription factor 4, belongs to class V of the transcription family. The expression of these two proteins exhibits a dynamic pattern with regard to their expression sites and levels. The aim of this study was to investigate the role of de novo methylation in the regulation of the tissue- and site-specific expression of these proteins. The dynamics of the de novo methylation of 15 CpGs and six CpGs in Sox9 and Oct4 respectively, was studied with sodium bisulfite genomic DNA sequencing in mouse testis at different developmental stages. Consistent methylation of three CpGs was observed in adult ovary in which the expression of Sox9 was feeble, while the level of methylation in somatic tissue was greater in Oct4 compared to germinal tissue. The promoter-chromatin status of Sox9 was also studied with a chromatin immune-precipitation assay.

Differential DNA methylation of vocal and facial anatomy genes in modern humans

“…In human skeletal samples, hypermethylation of the SOX9 promoter was shown to downregulate its activity, and consequently its targets 24 . This was also demonstrated repeatedly in non-skeletal tissues of human 25,26 and mouse 27,28 . We found substantial hypermethylation in AMHs in the following regions: (a) the SOX9 promoter; (b) seven of its proximal and distal skeletal and skeletal progenitor enhancers 23 ; (c) the targets of SOX9: ACAN (DMR #80) and COL2A1 (DMR #1, the most significant AMH-derived DMR, which spans 32 kb and covers almost the entire COL2A1 gene, from its 1st intron to its 54th exon and 3′UTR region); and (d) an upstream lincRNA (LINC02097).…”

Loss of Dnmt3b in Chondrocytes Leads to Delayed Endochondral Ossification and Fracture Repair

“…Additionally, Weber and colleagues demonstrated that there are two distinct promoters in the genome, the strong CpG island promoter and weak CpG island promoter, which can differently regulate gene expression through DNA methylation; eg, the gene can be suppressed although strong CpG island promoter is unmethylated. Furthermore, Dr. Sachan's group (Pamnani and colleagues)reported that even within the same promoter, the single CpG island methylation (six in total) cannot correlate with Oct4 gene expression during testicular development. Because we only detect the methylation in a single CpG island in Cxcl12 gene, our data cannot provide comprehensive insight into the effect of DNA methylation on Cxcl12 gene expression and cannot directly link a specific CpG site in the Cxcl12 with the gene expression profile.…”

Methylation Patterns of <b><i>SOX3, SOX9</i></b>, and <b><i>WNT4</i></b> Genes in Gonads of Dogs with XX (<b><i>SRY</i></b>-Negative) Disorder of Sexual Development

“…However, upregulation of this gene due to duplication [Rossi et al, 2014] or copy number variation in the upstream region [MarcinkowskaSwojak et al, 2015] is thought to be involved in XX DSD pathogenesis. Strong immunohistochemical signals of the SOX9 protein were observed in fetal, neonatal, and normal adult canine testes [Banco et al, 2016], while Sox9 expression in adult mouse ovary was very low and transient [Notarnicola et al, 2006;Pamnani et al, 2016]. Therefore, hypomethylation of the SOX9 promoter in the studied dogs is not surprising.…”

“…CpG hypermethylation of SOX3 and its underexpression in penile carcinoma tissue were reported by Kuasne et al [2015]. Methylation of CpGI in the 5 ′ UTR of murine Sox9 showed different profiles in testis and ovaries [Pamnani et al, 2016]. To the best of our knowledge, such analysis has not been carried out for the mammalian WNT4 gene.…”