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Long-range cis effects of ectopic X-inactivation centres on a mouse autosome - PubMed

  • ️Wed Jan 01 1997

. 1997 Mar 20;386(6622):275-9.

doi: 10.1038/386275a0.

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Long-range cis effects of ectopic X-inactivation centres on a mouse autosome

J T Lee et al. Nature. 1997.

Abstract

In mammals, the X chromosome is unique in being capable of complete inactivation. Such X inactivation evolved to compensate for gene dosage differences between females with two X chromosomes and males with one. Transcriptional silencing of a single female X chromosome is controlled in cis by Xist, whose RNA product coats the inactive X chromosome (Xi), and the X-inactivation centre (Xic). A transgenic study limited the Xic to 450 kilobases including Xist, and demonstrated that it is sufficient to initiate X inactivation. Here we report that ectopic Xist RNA completely coats transgenic chromosome 12. Expression of genes over 50 centimorgans was reduced two-fold and was detected only from the normal homologue in fibroblasts. Moreover, ectopic Xic action resulted in chromosome-wide changes that are characteristic of the X(i): DNA replication was delayed, and histone H4 was markedly hypoacetylated. Our findings suggest long-range cis effects on the autosome similar to those of X inactivation, and imply that the Xic can both initiate X inactivation and drive heterochromatin formation. Thus, the potential for chromosome-wide gene regulation is not intrinsic to X-chromosome DNA, but can also occur on autosomes possessing the Xic.

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Comment in

  • Remodelling chromatin with RNA.

    Willard HF, Salz HK. Willard HF, et al. Nature. 1997 Mar 20;386(6622):228-9. doi: 10.1038/386228a0. Nature. 1997. PMID: 9069277 No abstract available.

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