Methylation-dependent and independent regulatory regions in the Na,K-ATPase alpha4 (Atp1a4) gene may impact its testis-specific expression

Gene
Deepti L KumarPaul F James

Abstract

The α4 Na,K-ATPase is a sperm-specific protein essential for sperm motility and fertility yet little is known about the mechanisms that regulate its expression in germ cells. Here, the potential involvement of DNA methylation in regulating the expression of this sperm-specific protein is explored. A single, intragenic CpG island (Mα4-CGI) was identified in the gene encoding the mouse α4 Na,K-ATPase (Atp1a4), which displayed reduced methylation in mouse sperm (cells that contain α4) compared to mouse kidney (tissue that lacks α4 expression). Unlike the intragenic CGI, the putative promoter (the -700 to +200 region relative to the transcriptional start site) of Atp1a4 did not show differential methylation between kidney and sperm nevertheless it did drive methylation-dependent reporter gene expression in the male germ cell line GC-1spg. Furthermore, treatment of GC-1spg cells with 5-aza2-deoxycytidine led to upregulation of the α4 transcript and decreased methylation of both the Atp1a4 promoter and the Mα4-CGI. In addition, Atp1a4 expression in mouse embryonic stem cells deficient in DNA methyltransferases suggests that both maintenance and de novo methylation are involved in regulating its expression. In an attempt to define the...Continue Reading

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Citations

Jan 5, 2018·Toxicological Sciences : an Official Journal of the Society of Toxicology·Yousuke WatanabeMakoto Shibutani
May 12, 2016·American Journal of Physiology. Endocrinology and Metabolism·Sergej Pirkmajer, Alexander V Chibalin

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