A role for non-coding Tsix transcription in partitioning chromatin domains within the mouse X-inactivation centre

<p>Abstract</p> <p>Background</p> <p>Delimiting distinct chromatin domains is essential for temporal and spatial regulation of gene expression. Within the X-inactivation centre region (<it>Xic</it>), the <it>Xist </it>locus, which triggers X-inactivation, is juxtaposed to a large domain of H3K27 trimethylation (H3K27me3).</p> <p>Results</p> <p>We describe here that developmentally regulated transcription of <it>Tsix</it>, a crucial non-coding antisense to <it>Xist</it>, is required to block the spreading of the H3K27me3 domain to the adjacent H3K4me2-rich <it>Xist </it>region. Analyses of a series of distinct <it>Tsix </it>mutations suggest that the underlying mechanism involves the RNA Polymerase II accumulating at the <it>Tsix </it>3'-end. Furthermore, we report additional unexpected long-range effects of <it>Tsix </it>on the distal sub-region of the <it>Xic</it>, involved in <it>Xic</it>-<it>Xic </it>trans-interactions.</p> <p>Conclusion</p> <p>These data point toward a role for transcription of non-coding RNAs as a developmental strategy for the establishment of functionally distinct domains within the mammalian genome.</p

Nuclear mRNA Degradation Pathway(s) Are Implicated in Xist Regulation and X Chromosome Inactivation

A critical step in X-chromosome inactivation (XCI), which results in the dosage compensation of X-linked gene expression in mammals, is the coating of the presumptive inactive X chromosome by the large noncoding Xist RNA, which then leads to the recruitment of other factors essential for the heterochromatinisation of the inactive X and its transcriptional silencing. In an approach aimed at identifying genes implicated in the X-inactivation process by comparative transcriptional profiling of female and male mouse gastrula, we identified the Eif1 gene involved in translation initiation and RNA degradation. We show here that female embryonic stem cell lines, silenced by RNA interference for the Eif1 gene, are unable to form Xist RNA domains upon differentiation and fail to undergo X-inactivation. To probe further an effect involving RNA degradation pathways, the inhibition by RNA interference of Rent1, a factor essential for nonsense-mediated decay and Exosc10, a specific nuclear component of the exosome, was analysed and shown to similarly impair Xist upregulation and XCI. In Eif1-, Rent1-, and Exosc10-interfered clones, Xist spliced form(s) are strongly downregulated, while the levels of unspliced form(s) of Xist and the stability of Xist RNA remain comparable to that of the control cell lines. Our data suggests a role for mRNA nuclear degradation pathways in the critical regulation of spliced Xist mRNA levels and the onset of the X-inactivation process

Dernières nouvelles du chromosome X

L’inactivation d’un des deux chromosomes X des femelles mammifères est un processus vital et emblématique des régulations épigénétiques. Elle est déclenchée par l’accumulation d’un ARN non codant, XIST, qui isole le chromosome concerné de la machinerie transcriptionnelle ; l’état inactif persiste ensuite de manière stable au cours des divisions cellulaires successives. Cependant, des découvertes récentes conduisent à revisiter certains principes généraux de l’inactivation du chromosome X initialement établis. Ainsi le chercheur, tout comme le poète*

Archaeological research into the Islamic period in Yemen. Preliminary notes on the French Expedition 1993

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Al-Shihr and the southern coast of Yemen : preliminary notes on the French archaelogical expedition

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