CORRELATION BETWEEN HYPOMETHYLATION OF DNA AND EXPRESSION OF GLOBIN GENES IN FRIEND ERYTHROLEUKEMIA CELLS
CORRELATION BETWEEN HYPOMETHYLATION OF DNA AND EXPRESSION OF GLOBIN GENES IN FRIEND ERYTHROLEUKEMIA CELLS
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DOI：
10.1111/j.1432-1033.1977.tb11926.x
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发表时间：
1977-01-01
期刊：
影响因子：
--
通讯作者：
ACS, G
中科院分区：
文献类型：
--
作者：
CHRISTMAN, JK;PRICE, P;ACS, G
L-乙硫氨酸是小鼠红白血病细胞分化的诱导剂。当Friend红白血病[FL]细胞在4 mM L-乙硫氨酸的存在下生长时，珠蛋白mRNA积累，在4-5天内，培养的细胞中25-30%的细胞含有Hb。用溴脱氧尿苷孵育细胞可阻止乙硫氨酸诱导的珠蛋白mRNA积聚和红系分化。在L-乙硫氨酸作为FL细胞分化诱导剂的浓度下，它抑制体内dna和tRNA的甲基化，但不阻止大分子合成或细胞分裂。为了确定FL细胞中特定甲基转移酶的抑制和珠蛋白合成的激活之间是否存在联系，检测了FL细胞DNA和tRNA在二甲基亚砜[Me2SO]和丁酸盐诱导分化过程中的低甲基化程度。与乙硫氨酸处理细胞的tRNA相反，丁酸盐或Me2SO诱导的细胞tRNA不能在体外使用同源酶甲基化。与未诱导的细胞DNA相比，暴露于3种诱导剂的细胞中分离的DNA甲基化程度显著降低。DNA甲基化可能在基因表达调控中发挥作用。
L-Ethionine was identified as an inducer of differentiation in mouse erythroleukemia cells. When Friend erythroleukemia [FL] cells are grown in the presence of 4 mM L-ethionine, globin mRNA accumulates and in 4-5 days, 25-30% of the cells in the culture contain Hb. Incubation of the cells with bromodeoxyuridine prevents ethionine-induced accumulation of globin mRNA and erythroid differentiation. At the concentration where L-ethionine acts as an inducer of FL cell differentiation it inhibits methylation of DNA and tRNA in vivo but does not prevent macromolecular synthesis or cell division. To establish whether a link existed between inhibition of a specific methyltransferase and activation of globin synthesis in FL cells, the degree of hypomethylation of DNA and tRNA from FL cells induced to differentiate with dimethylsulfoxide [Me2SO] and butyrate was examined. In contrast to the tRNA from ethionine-treated cells, tRNA from cells induced by butyrate or Me2SO cannot be methylated in vitro using homologous enzymes. DNA isolated from cells exposed to any of the 3 inducers was significantly hypomethylated when compared with DNA from uninduced cells. Methylation of DNA may play a role in the regulation of gene expression.