Functional intergenic transcription: a case study of the X-inactivation centre

Long known to be riddled with repetitive elements and regarded as 'junk', intergenic regions in the mammalian genome now appear to be more than incidental spacers between coding sequences. Here, I review the example of Xite, an intergenic region at the X-inactivation centre which was recently shown to regulate the X-chromosome choice decision. Xite contains a series of DNaseI-hypersensitive sites and harbours two intergenic transcription start sites. These intergenic transcription elements act at the onset of X-chromosome inactivation (XCI) to bias the selection of the active X. It has been proposed that Xite acts in cis on Tsix by promoting its persistence during XCI. Xite has also been proposed to be a candidate for the X-controlling element, a naturally occurring modifier of XCI ratios in mice and possibly also in humans. It seems likely that intergenic transcription will turn out to be a widespread phenomenon in mammals and that, more importantly, it will emerge as a significant regulatory mechanism for the expression of coding sequences.