A chromosome 11-linked determinant controls fetal globin expression and the fetal-to-adult globin switch.
A chromosome 11-linked determinant controls fetal globin expression and the fetal-to-adult globin switch.
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11 号染色体连锁决定簇控制胎儿珠蛋白表达和胎儿到成人珠蛋白的转换。
DOI：
10.1073/pnas.84.22.8105
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发表时间：
1987
影响因子：
11.1
通讯作者：
Stamatoyannopoulos,G
中科院分区：
文献类型：
--
作者：
Melis,M;Demopulos,G;Najfeld,V;Zhang,JW;Brice,M;Papayannopoulou,T;Stamatoyannopoulos,G
小鼠红白血病（MEL）细胞与人胎儿红系细胞融合形成的杂交体产生人胎儿珠蛋白，但随着培养时间的推移，它们会转变为成人珠蛋白的生产。为了获得控制γ-β转换的元件的染色体分配的信息，我们分析了仅产生或主要产生人胎儿珠蛋白的杂交种和仅产生成人珠蛋白的杂交种的染色体组成。没有人的染色体是一贯存在于表达胎儿珠蛋白的杂交种和一贯缺乏表达成人珠蛋白的杂交种。亚克隆实验表明，在显示胎儿珠蛋白程序的亚克隆和那些已切换到成人珠蛋白程序的表达的亚克隆中，染色体组成相同。这些数据表明仅保留一个人染色体，11号染色体--足以表达人类胎儿珠蛋白和随后的γ-β转换。结果表明，γ-β开关控制顺式β-珠蛋白基因座或反式作用机制，其基因驻留在人类11号染色体。
Hybrids formed by fusing mouse erythroleukemia (MEL) cells with human fetal erythroid cells produce human fetal globin, but they switch to adult globin production as culture time advances. To obtain information on the chromosomal assignment of the elements that control gamma-to-beta switching, we analyzed the chromosomal composition of hybrids producing exclusively or predominantly human fetal globin and hybrids producing only adult human globin. No human chromosome was consistently present in hybrids expressing fetal globin and consistently absent in hybrids expressing adult globin. Subcloning experiments demonstrated identical chromosomal compositions in subclones displaying the fetal globin program and those that had switched to expression of the adult globin program. These data indicate that retention of only one human chromosome-i.e., chromosome 11--sufficient for expression of human fetal globin and the subsequent gamma-to-beta switch. The results suggest that the gamma-to-beta switch is controlled either cis to the beta-globin locus or by a trans-acting mechanism, the genes of which reside on human chromosome 11.