Rifkind R A, Sheffery M, Profous-Juchelka H R, Reuben R C, Marks P A
Prog Clin Biol Res. 1983;134:183-92.
We can provide increasing insight, albeit still incomplete, into the changes in MELC that accompany induced globin gene expression. It is suggested that these transformed CFU-E-like erythroid precursor cells exhibit in their uninduced state a DNA methylation pattern and globin gene chromatin configuration (DNase I sensitivity) that is compatible with actual or potential gene transcription. Such features may reflect alterations in chromatin configuration that occurred earlier, during the differentiation of erythroid precursor cells, which is associated with the restriction in developmental potential that is characteristic of progression to the CFU-E (or MELC) stage of erythropoiesis. Uninduced MELC display a low level of globin gene transcription, producing globin mRNA or mRNA precursors whose processing or stabilization is the site of action of hemin. The major increase in MELC globin gene transcription that is initiated by HMBA or butyric acid is accompanied by an increase in DNase I hypersensitivity in the regions 5' to the active globin genes. This suggests that reorganization of chromatin structure in the globin gene domains is associated with accelerated globin gene transcription and may be characteristic of a developmental stage transition during terminal differentiation in the erythroid cell lineage.
我们能够对伴随诱导珠蛋白基因表达的MELC变化提供越来越深入的见解，尽管仍不完整。有人提出，这些转化的CFU-E样红系前体细胞在未诱导状态下表现出与实际或潜在基因转录相容的DNA甲基化模式和珠蛋白基因染色质构型（DNase I敏感性）。这些特征可能反映了在红系前体细胞分化过程中早期发生的染色质构型改变，这与向红系造血的CFU-E（或MELC）阶段进展所特有的发育潜能限制有关。未诱导的MELC显示出低水平的珠蛋白基因转录，产生珠蛋白mRNA或mRNA前体，其加工或稳定是血红素的作用位点。由HMBA或丁酸引发的MELC珠蛋白基因转录的主要增加伴随着活性珠蛋白基因5'区域DNase I超敏性的增加。这表明珠蛋白基因结构域中染色质结构的重组与加速的珠蛋白基因转录相关，并且可能是红系细胞谱系终末分化过程中发育阶段转变的特征。
