Enox, a novel gene that maps 10 kb upstream of Xist and partially escapes X inactivation

Dosage compensation in mammals is accomplished by the transcriptional silencing of a single X chromosome in female cells, a process termed X inactivation. A cytogenetically defined region of the X chromosome, the X-inactivation center (Xic), is necessary in cis for this process. Although the precise nature of the Xic remains unknown, a key component, the Xist gene, has been shown to be essential for X inactivation. In XX somatic cells, Xist RNA is specifically transcribed from the inactive X chromosome, which is otherwise essentially heterochromatic. Previous studies aimed at defining the proximal limit of the Xic have indicated that it lies within 30 kb upstream of the Xist promoter. Here we describe a novel gene, Enox (expressed neighbor of Xist), that maps to an unmethylated CpG island 10 kb upstream of Xist. Enox transcripts are antisense relative to Xist, highly heterogeneous, and apparently noncoding. In female somatic tissue Enox partially escapes from X inactivation. We discuss the implications of these findings in relation to our understanding of the Xic.