REACTIVATION OF AN INACTIVE HUMAN X-CHROMOSOME - EVIDENCE FOR X INACTIVATION BY DNA METHYLATION
REACTIVATION OF AN INACTIVE HUMAN X-CHROMOSOME - EVIDENCE FOR X INACTIVATION BY DNA METHYLATION
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DOI：
10.1126/science.6164095
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发表时间：
1981-01-01
期刊：
影响因子：
56.9
通讯作者：
SHAPIRO, LJ
中科院分区：
文献类型：
--
作者：
MOHANDAS, T;SPARKES, RS;SHAPIRO, LJ
分离到一个次黄嘌呤-鸟嘌呤磷酸核糖转移酶（HPRT）缺陷的小鼠-人体细胞杂交克隆，该克隆含有一个结构正常的失活的人X染色体。用5-氮杂胞苷处理杂交细胞，并测试人X连锁基因的再活化和表达。5-氮杂胞苷处理后HPRT阳性克隆的频率比未处理的杂交细胞中观察到的频率高1000倍。分离14个独立的HPRT阳性克隆并分析人X标记物的表达。等电聚焦显示这些克隆中表达的HPRT是人的。14个克隆中的一个表达人葡萄糖-6-磷酸脱氢酶，另一个表达人磷酸甘油酸激酶。由于5-氮杂胞苷处理导致DNA低甲基化，DNA甲基化可能是人类X染色体失活的机制。
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-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.