Poster Sessions

TRANS-6

Alan Pang

A. L. Y. Pang, J. Fang, S. Peacock, O. M. Rennert, W. Y. Chan

Transcriptional regulation of a novel N-acetyltransferase subunit gene in the mouse testis

N-terminal protein acetylation is a co-translational modification process occurring on many eukaryotic proteins. The enzyme responsible for this process, N-terminal acetyltransferase, is composed of the catalytic subunit Ard1 and auxiliary subunit Nat1. We cloned and characterized Ard2, a novel mouse testis-predominant homolog of Ard1. The genomic organization and expression characteristics of Ard2 indicate it is a retrotransposed copy of the X-linked Ard1. Similar to Ard1, Ard2 can interact with Nat1 to reconstitute a functional N-terminal acetyltransferase. We found that transcription of Ard2 in developing male germ cells in vivo is correlated with progressive demethylation of the CpG islands spanning the proximal promoter and coding region of the gene. In contrast, somatic tissues and cells that do not express Ard2 display extensive methylation of the region. Consistent with the role of DNA methylation in repression of gene transcription, DNA demethylation induced by 5-aza-2’-deoxycytidine treatment alone is sufficient to reactivate Ard2 expression in non-expressing cells. Our results indicate DNA methylation is involved in the spatial and temporal control of Ard2 expression during male germ cell development. The involvement of other genetic factors in Ard2 transcription activation is now under investigation.