Localized Derepression on the Human Inactive X Chromosone in Mouse-Human Cell Hybrids.
Localized Derepression on the Human Inactive X Chromosone in Mouse-Human Cell Hybrids.
复制标题
小鼠-人类细胞杂交体中人类无活性 X 染色体的局部去抑制。
DOI：
10.1073/pnas.72.4.1510
复制
发表时间：
1975
影响因子：
11.1
通讯作者：
R. Demars
中科院分区：
文献类型：
--
作者：
B. Kahan;R. Demars
次黄嘌呤磷酸核糖基转移酶(HPRT；IMP：焦磷酸核糖基转移酶，EC 2.4.2.8)基因在人失活X染色体上失活的证据在小鼠和人类细胞的杂交中获得。小鼠细胞缺乏HPRT，也缺乏腺嘌呤磷酸核糖转移酶(APRT；AMP：焦磷酸核糖转移酶；EC2.4.2.7)。人类女性成纤维细胞由于活性X上的突变而缺乏HPRT，但在非活性X上含有正常的HPRT基因。这两条人类X染色体通过形态上的差异进一步区分：非活性X在形态上是正常的，而活性X包括大多数常染色体1的长臂移位到X长臂的末端。首先通过选择分离了41个存在APRT的杂交克隆；当这些克隆被选择用于HPRT时，其中6个产生了具有人HPRT的衍生物，发生率约为10-6个APRT选择的杂交细胞中的1个。HPRT阳性的衍生物含有一个看起来正常的X染色体，与亲代人成纤维细胞的不活跃的X染色体没有区别。在所有HPRT阳性的杂交细胞中均未发现具有易位的活性X。人磷酸甘油激酶(ATP：3-磷酸-D-甘油酸1-磷酸转移酶。(EC 2.7.2.3)和葡萄糖-6-磷酸脱氢酶(D-葡萄糖-6-磷酸：NADP-1-氧化还原酶，EC 1.1.1.49)在表达HPRT的杂交种中未检测到，尽管它们含有明显完整的X染色体。这些观察结果最简单的解释是，包括HPRT基因座但不包括磷酸甘油激酶和葡萄糖-6-磷酸脱氢酶基因座的不活跃X染色体片段的罕见、稳定的去抑制。
Evidence for derepression of the gene for hypoxanthine phosphoribosyltransferase (HPRT; IMP: pyrophosphate phosphoribosyltransferase, EC 2.4.2.8) on the human inactive X chromosome was obtained in hybrids of mouse and human cells. The mouse cells lacked HPRT and were also deficient in adenine phosphoribosyltransferase (APRT; AMP: pyrophosphate phosphoribosyltransferase; EC2.4.2.7). The human female fibroblasts were HPRT-deficient as a consequence of a mutation on the active X but contained a normal HPRT gene on the inactive X. The two human X chromosomes were further distinguished by differences in morphology: the inactive X was morphologically normal while the active X included most of the long arm of autosome no. 1 translocated to the distal end of the X long arm. Forty-one hybrid clones were first isolated by selection for the presence of APRT; when these clones were selected for HPRT, six of them yielded derivatives having human HPRT with incidences of about 1 in 10-6 APRT-selected hybrid cells. The HPRT-positive derivatives contained a normal-appearing X chromosome indistinguishable from the inactive X of the parental human fibroblasts. The active X with the translocation was not found in any of the HPRT-positive hybrid cells. Human phosphoglycerokinase (ATP:3-phospho-D-glycerate 1-phosphotransferase. EC 2.7.2.3) and glucose-6-phosphate dehydrogenase (D-glucose 6-phosphate: NADP 1-oxidoreductase, EC 1.1.1.49), which are specified by X-chromosomal loci, were not detected in the hybrids expressing HPRT even though they contained an apparently intact X chromosome. The observations are most simply explained by the infrequent, stable derepression of inactive X chromosome segments that include the HPRT locus but not the phosphoglycerokinase and glucose-6-phosphate dehydrogenase loci.