Zavodny P J, Roginski R S, Skoultchi A I
Prog Clin Biol Res. 1983;134:53-62.
The expression of human globin genes and intergenic DNA is being investigated in MEL-human hybrids containing intact human chromosomes derived from nonerythroid cells. The studies indicate that a factor(s) present in MEL cells can cause activation of both beta- and gamma-globin genes that can be further stimulated by treatment with DMSO, an inducer of MEL cell differentiation. MEL-lymphoblast and MEL-fibroblast hybrids express an adult-like program in which much larger amounts of beta-globin mRNA than gamma-globin mRNA are produced; human beta-globin is at least as efficient as mouse beta-globin gene expression. The expression of both beta- and gamma-globin genes appears to be normal, as their mRNAs were found in polyribosomes and human beta-globin chains were readily detected. These results suggest that the MEL cells may be exploited as recipients of human globin genes for studies of molecular mechanisms controlling their expression. Comparison of intergenic DNA transcription patterns in hybrids and other cells not expressing human beta-globin has led to the identification of two regions flanking the delta-beta-globin locus whose transcription is correlated with beta-globin. One region 3' to the beta gene may define the site where its transcription terminates. Transcription of the other region, which is 5' to the delta gene, may be involved in some unknown way in hemoglobin switching.
在含有源自非红细胞系细胞的完整人类染色体的MEL-人类杂交细胞中，正在研究人类珠蛋白基因和基因间DNA的表达。研究表明，MEL细胞中存在的一种或多种因子可导致β-珠蛋白基因和γ-珠蛋白基因的激活，用二甲基亚砜（一种MEL细胞分化诱导剂）处理可进一步刺激这种激活。MEL-淋巴母细胞和MEL-成纤维细胞杂交细胞表达一种类似成人的程序，其中产生的β-珠蛋白mRNA比γ-珠蛋白mRNA多得多；人类β-珠蛋白基因的表达效率至少与小鼠β-珠蛋白基因相同。β-珠蛋白基因和γ-珠蛋白基因的表达似乎都是正常的，因为在多核糖体中发现了它们的mRNA，并且很容易检测到人类β-珠蛋白链。这些结果表明，MEL细胞可被用作人类珠蛋白基因的受体，用于研究控制其表达的分子机制。通过比较杂交细胞和其他不表达人类β-珠蛋白的细胞中的基因间DNA转录模式，已鉴定出δ-β-珠蛋白基因座两侧的两个区域，其转录与β-珠蛋白相关。β基因3'端的一个区域可能定义了其转录终止的位点。另一个区域位于δ基因的5'端，其转录可能以某种未知方式参与血红蛋白转换。
