Antisense regulation in X inactivation and autosomal imprinting

Abstract

The regulation of epigenetic phenomena by elements encoding antisense RNA's is one of the most rapidly emerging themes in mammalian gene expression. Such regulation is epitomized by X chromosome inactivation (XCI) and autosomal imprinting. In XCI, TSIX serves as an antisense regulator of XIST, the silencer element for XCI which itself makes a non-coding transcript. Numerous antisense transcripts have also been discovered in autosomally imprinted loci, including the IGF2R/AIR locus, the Prader-Willi/Angelman Syndrome (PWS/AS) locus, and the Beckwith-Wiedemann Syndrome (BWS) locus. How these antisense elements regulate XCI and imprinting remains unsolved. However, various structural and functional similarities among them imply the possibility of shared mechanism. Among the most interesting are the antagonistic relationship between sense and antisense loci and the initiation of antisense transcripts within imprinting centers. This article reviews the latest developments in antisense regulation in XCI and autosomal imprinting and speculates on molecular means by which antisense genes can regulate silencing in mammals.