Role of the Xist gene in X chromosome choosing

York Marahrens, Jan Loring, Rudolf Jaenisch

Research output: Contribution to journalArticlepeer-review

122 Scopus citations

Abstract

In female mammals a 'random choice' mechanism decides which of the two X chromosomes will be inactivated. It has been postulated that Xist is crucial for heterochromatinization and thus functions downstream of the choice mechanism. Here we report that females heterozygous for an internal deletion in the Xist gene, which includes part of exon 1 and extends to exon 5, undergo primary nonrandom inactivation of the wild-type X chromosome. The Xist gene, therefore, not only has a role in chromatin remodeling, but also includes an element required for X chromosome choosing. In conflict with the prevailing view of how choosing occurs, the element identified by the deletion plays a positive role in the choice mechanism and forces a reassessment of how X chromosome choosing is thought to occur.

Original languageEnglish (US)
Pages (from-to)657-664
Number of pages8
JournalCell
Volume92
Issue number5
DOIs
StatePublished - Mar 6 1998
Externally publishedYes

Bibliographical note

Funding Information:
We would like to thank Barbara Panning and Györgyi Csankovszki for much helpful technical advice. We would also like to thank Ruth Curry for excellent technical assistance, Györgyi Csankovszki for providing plasmids and probes, and Laura Gammill and Mary Ellen Lane for critical reading of the manuscript. This work was supported by a grant from the National Institutes of Health/National Cancer Institute (R35-CA44339) to R. J. During the course of this work, Y. M. was supported by the Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation Fellowship, DRG-1292, and a Postdoctoral Fellowship of the Merck/MIT Collaboration.

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