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Science 23 January 1981:
Vol. 211. no. 4480, pp. 393 - 396
DOI: 10.1126/science.6164095
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Articles

Science, Vol 211, Issue 4480, 393-396
Copyright © 1981 by American Association for the Advancement of Science

articles

Reactivation of an inactive human X chromosome: evidence for X inactivation by DNA methylation

T Mohandas, RS Sparkes, and LJ Shapiro

A mouse-human somatic cell hybrid clone, deficient in hypoxanthine-guanine phosphoribosyltransferase (HPRT) and containing a structurally normal inactive human X chromosome, was isolated. The hybrid cells were treated with 5-azacytidine and tested for the reactivation and expression of human X-linked genes. The frequency of HPRT-positives clones after 5-azacytidine treatment was 1000-fold greater than that observed in untreated hybrid cells. Fourteen independent HPRT-positive clones were isolated and analyzed for the expression of human X markers. Isoelectric focusing showed that the HPRT expressed in these clones is human. One of the 14 clones expressed human glucose-6-phosphate dehydrogenase and another expressed human phosphoglycerate kinase. Since 5-azacytidine treatment results in hypomethylation of DNA, DNA methylation may be a mechanism of human X chromosome inactivation.


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