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Chapter 44,148

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

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

Science 211(4480): 393-396

1981

ISSN/ISBN: 0036-8075
PMID: 6164095
DOI: 10.1126/science.6164095
Accession: 044147160
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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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Related References

Mohandas, T.; Sparkes, R.S.; Shapiro, L.J. 1980: Reactivation of the inactive human x chromosome evidence for dna methylation as a molecular mechanism of x inactivation American Journal of Human Genetics 32(6): 159A
Jagiello, G.; Tantravahi, U.; Ducayen, M.; Erlanger, B. 1986: Immunocytochemical evidence for methylation of the inactive x chromosome in human oogonia Journal of Cell Biology 103(5 Part 2): 247A
Jagiello, G.M.; Tantravahi, U.; Ducayen, M.B.; Erlanger, B.F. 1987: Immunocytochemical evidence for methylation of the inactive X chromosome in human fetal oogonia Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine 186(2): 223-228
Mohandas, T.; Sparkes, R.S.; Shapiro, L.J. 1982: Genetic evidence for the inactivation of a human autosomal locus attached to an inactive X chromosome American Journal of Human Genetics 34(5): 811-817
Lock, L.F.; Takagi, N.; Martin, G.R. 1987: Methylation of the Hprt gene on the inactive X occurs after chromosome inactivation Cell 48(1): 39-46
Mohandas, T.K.; Salido, E.C.; Passage, M.B.; Yen, P.H.; Shapiro, L.J. 1992: An evaluation of the inactive mouse X chromosome in somatic cell hybrids Further evidence for differences in human and mouse X-inactivation American Journal of Human Genetics 51(4 Suppl): A115
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