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Molecular and Cellular Biology, April 1999, p. 3156-3166, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Xist Yeast Artificial Chromosome Transgenes Function as X-Inactivation Centers Only in Multicopy Arrays and Not as Single Copies

Edith Heard,1,* Fabien Mongelard,2 Danielle Arnaud,1 and Philip Avner1

Unité de Génétique Moléculaire Murine, CNRS URA 1968, Institut Pasteur, F-75724 Paris Cedex 15,1 and Equipe Dyogen, Institut Albert Bonniot, Faculté de Médecine, 38706 La Tronche Cedex,2 France

Received 20 July 1998/Returned for modification 2 September 1998/Accepted 17 December 1998

X-chromosome inactivation in female mammals is controlled by the X-inactivation center (Xic). This locus is required for inactivation in cis and is thought to be involved in the counting process which ensures that only a single X chromosome remains active per diploid cell. The Xist gene maps to the Xic region and has been shown to be essential for inactivation in cis. Transgenesis represents a stringent test for defining the minimal region that can carry out the functions attributed to the Xic. Although YAC and cosmid Xist-containing transgenes have previously been reported to be capable of cis inactivation and counting, the transgenes were all present as multicopy arrays and it was unclear to what extent individual copies are functional. Using two different yeast artificial chromosomes (YACs), we have found that single-copy transgenes, unlike multicopy arrays, can induce neither inactivation in cis nor counting. These results demonstrate that despite their large size and the presence of Xist, the YACs that we have tested lack sequences critical for autonomous function with respect to X inactivation.

* Corresponding author. Mailing address: Unité de Génétique Moléculaire Murine, CNRS URA 1968, Institut Pasteur, 25 rue du Docteur Roux, F-75724 Paris Cedex 15, France. Phone: 33 1 456 88653. Fax: 33 1 456 88656. E-mail: eheard{at}pasteur.fr.

Molecular and Cellular Biology, April 1999, p. 3156-3166, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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