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

Abstract：

: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.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Sun BK,Deaton AM,Lee JT

doi

10.1016/j.molcel.2006.01.028

subject

Has Abstract

pub_date

2006-03-03 00:00:00

pages

617-28

issue

5

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(06)00050-5

journal_volume

21

pub_type

杂志文章

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