Coordinated transcriptional regulation of calmegin, a testis-specific molecular chaperon, by histone deacetylase and CpG methyltransferase

ABSTRACT

Calmegin is a testis-specific molecular chaperon playing a key role in spermatogenesis. However, the transcriptional regulatory mechanisms for calmegin expression are entirely unknown. Herein, we revealed that calmegin is transcriptionally regulated by histone deacetylase (HDAC) and CpG methyltransferase. The cDNA microarray analysis of the human fibrosarcoma cells treated with trichostatin A (TSA) showed an increased level of calmegin mRNA. The induction of calmegin mRNA by TSA was added by the treatment with 5-aza-2'-deoxycytidine (5'Aza- dC), implying that epigenetic alterations are involved in the transcriptional repression of the gene. Moreover, chromatin immunoprecipitation assay using an anti-acetyl-histone H3 antibody exhibited that the proximal region (-152~-31) of the calmegin promoter is responsible for HDAC-mediated transcriptional repression of the gene. These results demonstrate that calmegin expression is regulated by HDAC and CpG methyltransferase in a coordinative way.