Characterization of the Genomic Xist Locus in Rodents Reveals Conservation of Overall Gene Structure and Tandem Repeats but Rapid Evolution of Unique Sequence

Abstract

The Xist locus plays a central role in the regulation of X chromosome inactivation in mammals, although its exact mode of action remains to be elucidated. Evolutionary studies are important in identifying conserved genomic regions and defining their possible function. Here we report cloning, sequence analysis, and detailed characterization of the Xist gene from four closely related species of common vole (field mouse), Microtus arvalis. Our analysis reveals that there is overall conservation of Xist gene structure both between different vole species and relative to mouse and human Xist/XIST. Within transcribed sequence, there is significant conservation over five short regions of unique sequence and also over Xist-specific tandem repeats. The majority of unique sequences, however, are evolving at an unexpectedly high rate. This is also evident from analysis of flanking sequences, which reveals a very high rate of rearrangement and invasion of dispersed repeats. We discuss these results in the context of Xist gene function and evolution.

The recruitment of chromatin modifiers by long noncoding RNAs: lessons from PRC2

“…The A-repeat in Xist and RepA RNA is evolutionary conserved (Nesterova et al 2001;Maenner et al 2010). Hence, evolutionary conservation of HOTAIR and Xist elements that interact with PRC2 is an appealing hypothesis.…”

“…RepA lncRNA, like Xist, contains eight to nine short tandem repeats from the evolutionary conserved A-repeat region of the Xist locus (Nesterova et al 2001). Importantly, a short synthetic 28-nt RNA with the sequence of a single repeat from within the A-repeat region was shown to bind PRC2 in vitro (Zhao et al 2008).…”

The role of long non-coding RNAs in neurodevelopment, brain function and neurological disease

“…For example, several lncRNAs (i.e. Xist and Airn) with wellestablished epigenetic regulatory roles are poorly conserved between human and mouse at the primary sequence level [53,54]. Additionally, rapidly evolving lncRNAs that are lineage-specific likely represent recent evolutionary innovations.…”

X chromosome inactivation sparked by non-coding RNAs

“…Xist RNA contains six different direct sequence repeats. 12,19 Only the most 5'-located repeat A has been assigned a function. Its deletion disrupts silencing of X linked genes without impact on localization of Xist RNA to the X chromosome.…”