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

T. Mohandas; R. S. Sparkes; L. J. Shapiro

doi:10.1126/science.6164095

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

T. Mohandas, R. S. Sparkes, L. J. Shapiro

Research output: Contribution to journal › Article › peer-review

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Abstract

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 ofhuman X-linked genes. The frequency of HPRT-positive 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.

Original language	English
Pages (from-to)	393-396
Number of pages	4
Journal	Science
Volume	211
Issue number	4480
DOIs	https://doi.org/10.1126/science.6164095
State	Published - 1981

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@article{c69d955ef32e47598581e3a367b0c5ab,

title = "Reactivation of an inactive human X chromosome: Evidence for X inactivation by DNA methylation",

abstract = "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 ofhuman X-linked genes. The frequency of HPRT-positive 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.",

author = "T. Mohandas and Sparkes, {R. S.} and Shapiro, {L. J.}",

year = "1981",

doi = "10.1126/science.6164095",

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journal = "Science",

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TY - JOUR

T1 - Reactivation of an inactive human X chromosome

T2 - Evidence for X inactivation by DNA methylation

AU - Mohandas, T.

AU - Sparkes, R. S.

AU - Shapiro, L. J.

PY - 1981

Y1 - 1981

N2 - 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 ofhuman X-linked genes. The frequency of HPRT-positive 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.

AB - 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 ofhuman X-linked genes. The frequency of HPRT-positive 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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