X-chromosome inactivation (XCI), the dosage compensation process that equalizes X-linked gene expression between sexes, has mostly been studied in the mouse, where the central role for the non-coding RNA Xist in the initiation and spreading of the process was demonstrated. Although Xist is conserved in humans [1], very little is known concerning its regulation and function in this species. Several lines of evidence moreover suggest that different strategies have been adopted in the human to control XCI as compared to the mouse. In particular, in human pre-implantation development, XIST RNA coats the X chromosome(s) in both male and female embryos without inducing X-chromosome silencing [2]. This indicates that XIST expression and X-inactivation can be uncoupled during human embryogenesis and that other elements likely participate to the control of X chromosome activity in humans.XCI is established early during embryonic development, and embryonic stem cells can be used to decipher the kinetics and the molecular actors of the process. Human female embryonic stem cells (hESC) can be found in different configurations regarding XIST expression: most female hESC have already undergone XCI but tend to spontaneously lose XIST expression [3]. In the course of an RNA-seq analysis of female hESC, we identified an extended and un-annotated transcribed region producing a long unspliced, likely non-coding nuclear RNA. RNA-FISH analysis reveals that this transcript is expressed from, and coats the active X chromosome. We called this transcript XACT, for X-active coating transcript. In female hESC in which XIST is repressed, XACT is expressed from and coats both Xs, and this correlates with significant reactivation of the inactive X chromosome. Expression of XACT appears to be specific for pluripotent cells as its expression decreases during differentiation. Finally, we provide evidence that XACT is not conserved in the mouse.In conclusion, we have identified XACT as the first long ncRNA that coats the active X chromosome in human. Given its expression profile and lack of conservation, it is tempting to speculate that XACT is involved in the peculiar control of XCI initiation in human.

GC-biased gene conversion (gBGC) is a process associated with recombination that favors the transmission of GC alleles over AT alleles during meiosis. gBGC plays a major role in genome evolution in many eukaryotes. However, the molecular mechanisms of gBGC are still unknown. Different steps of the recombination process could potentially cause gBGC: the formation of double-strand breaks (DSBs), the invasion of the homologous or sister chromatid, and the repair of mismatches in heteroduplexes. To investigate these models, we analyzed a genome-wide data set of crossovers (COs) and noncrossovers (NCOs) in Saccharomyces cerevisiae. We demonstrate that the overtransmission of GC alleles is specific to COs and that it occurs among conversion tracts in which all alleles are converted from the same donor haplotype. Thus, gBGC results from a process that leads to long-patch repair. We show that gBGC is associated with longer tracts and that it is driven by the nature (GC or AT) of the alleles located at the extremities of the tract. These observations invalidate the hypotheses that gBGC is due to the base excision repair machinery or to a bias in DSB formation and suggest that in S. cerevisiae, gBGC is caused by the mismatch repair (MMR) system. We propose that the presence of nicks on both DNA strands during CO resolution could be the cause of the bias in MMR activity. Our observations are consistent with the hypothesis that gBGC is a nonadaptive consequence of a selective pressure to limit the mutation rate in mitotic cells.