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Publication : A transient heterochromatic state in Xist preempts X inactivation choice without RNA stabilization.

First Author  Sun BK Year  2006
Journal  Mol Cell Volume  21
Issue  5 Pages  617-28
PubMed ID  16507360 Mgi Jnum  J:108126
Mgi Id  MGI:3623063 Doi  10.1016/j.molcel.2006.01.028
Citation  Sun BK, et al. (2006) A transient heterochromatic state in Xist preempts X inactivation choice without RNA stabilization. Mol Cell 21(5):617-28
abstractText  X chromosome inactivation (XCI) depends on a noncoding sense-antisense transcript pair, Xist and Tsix. At the onset of XCI, Xist RNA accumulates on one of two Xs, coating and silencing the chromosome in cis. The molecular basis for monoallelic Xist upregulation is not known, though evidence predominantly supports a posttranscriptional mechanism through RNA stabilization. Here, we test whether Tsix RNA destabilizes Xist RNA. Unexpectedly, we find that Xist upregulation is not based on transcript stabilization at all but is instead controlled by transcription in a sex-specific manner. Tsix directly regulates its transcription. On the future inactive X, Tsix downregulation induces a transient heterochromatic state in Xist, followed paradoxically by high-level Xist expression. A Tsix-deficient X chromosome adopts the heterochromatic state in pre-XCI cells. This state persists through XCI establishment and 'reverts' to a euchromatic state during XCI maintenance. We have therefore identified chromatin marks that preempt and predict asymmetric Xist expression.
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