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

Nature volume 386, pages 275–279 (1997)Cite this article

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 one1. Transcriptional silencing of a single female X chromosome is controlled in cis by Xist2, whose RNA product coats the inactive X chromosome (Xi)3, and the X inactivation centre (Xic)4. A transgenic study limited the Xic to 450 kilobases including Xist, and demonstrated that it is sufficient to initiate X inactivation5. 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 Xi: 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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Authors and Affiliations

  1. Whitehead Institute for Biomedical Research, 9 Cambridge Centre, Cambridge, and Department of Biology, Massachusetts Institute of Technology, Massachusetts, 02142, USA

    Jeannie T. Lee & Rudolf Jaenisch

  2. Pathology Department, Massachusetts General Hospital, 15 Fruit Street, Boston, Massachusetts, 02114, USA

    Jeannie T. Lee

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  1. Jeannie T. Lee
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  2. Rudolf Jaenisch
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Lee, J., Jaenisch, R. Long-range cis effects of ectopic X-inactivation centres on a mouse autosome. Nature 386, 275–279 (1997). https://doi.org/10.1038/386275a0

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