Anderson W F, Chiang Y L, Sanders-Haigh L, Ley T J
Prog Clin Biol Res. 1983;134:39-52.
Fusions between somatic cell lines have previously yielded evidence for the existence of trans-acting gene regulatory factors. For this reason, we developed a cell line containing a "locked in" human 11-X translocation chromosome (containing the beta-globin-like gene cluster) in MEL cells. The human 11-X chromosome is stably integrated in the "M11-X" cell line, and single-copy human gamma and beta genes are present. After induction with HMBA, M11-X cells produced 500 copies per cell of correctly initiated, processed, and terminated human beta-globin mRNA; authentic human beta-globin chains were also produced at a low level. Despite the presence of normally arranged human gamma-globin genes, no gamma-globin mRNA could be detected after HMBA induction. However, cytosine residues near the gamma-globin gene promoters are completely methylated in these cells, suggesting that the gamma-globin genes may be repressed in part by DNA methylation. The pattern of human globin gene expression in M11-X cells may be affected by methylation and/or by trans-acting factors produced by these tetraploid cells.
体细胞系之间的融合此前已为反式作用基因调控因子的存在提供了证据。因此，我们构建了一种细胞系，该细胞系在MEL细胞中含有一条“锁定”的人类11号与X染色体的易位染色体（包含类β珠蛋白基因簇）。人类11号与X染色体稳定整合于“M11-X”细胞系中，且存在单拷贝的人类γ和β基因。用HMBA诱导后，M11-X细胞每个细胞产生500拷贝正确起始、加工和终止的人类β珠蛋白mRNA；也有少量真实的人类β珠蛋白链产生。尽管存在正常排列的人类γ珠蛋白基因，但HMBA诱导后未检测到γ珠蛋白mRNA。然而，这些细胞中γ珠蛋白基因启动子附近的胞嘧啶残基完全甲基化，这表明γ珠蛋白基因可能部分受到DNA甲基化的抑制。M11-X细胞中人类珠蛋白基因的表达模式可能受甲基化和/或这些四倍体细胞产生的反式作用因子的影响。
