Demethylation of the coding region triggers the activation of the human testis-specific PDHA2 gene in somatic tissues.

ABSTRACT: Human PDHA2 is a testis-specific gene that codes for the E(1)α subunit of Pyruvate Dehydrogenase Complex (PDC), a crucial enzyme system in cell energy metabolism. Since activation of the PDHA2 gene in somatic cells could be a new therapeutic approach for PDC deficiency, we aimed to identify the regulatory mechanisms underlying the human PDHA2 gene expression. Functional deletion studies revealed that the -122 to -6 promoter region is indispensable for basal expression of this TATA-less promoter, and suggested a role of an epigenetic program in the control of PDHA2 gene expression. Indeed, treatment of SH-SY5Y cells with the hypomethylating agent 5-Aza-2'-deoxycytidine (DAC) promoted the reactivation of the PDHA2 gene, by inducing the recruitment of the RNA polymerase II to the proximal pro

SUBMITTER: Pinheiro A 

PROVIDER: S-EPMC3365900 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature