Murine erythroleukemia cell differentiation: DNase I hypersensitivity and DNA methylation near the globin genes.

Murine erythroleukemia cell differentiation: DNase I hypersensitivity and DNA methylation near the globin genes.
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鼠红白血病细胞分化:DNase I 超敏反应和珠蛋白基因附近的 DNA 甲基化。

DOI:
10.1073/pnas.79.4.1180
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发表时间:
1982
影响因子:
11.1
通讯作者:
Marks,PA
Marks,PA
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Sheffery,M;Rifkind,RA;Marks,PA

文献摘要

被引文献

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在六亚甲基双乙酰胺(HMBA)介导的小鼠红白血病细胞(MELC)红系分化过程中,检测了含有α和β主珠蛋白基因的染色质对DNase I消化的敏感性以及这些基因附近的DNA甲基化模式。在未诱导和诱导的细胞中,含有α和β主要珠蛋白基因的染色质区域对DNA酶I的消化比含有在红系分化期间不表达的免疫球蛋白基因(IGα)的区域更敏感。然而,在低浓度的DNA酶I下,HMBA诱导分化的细胞中α和β主要球蛋白基因附近的染色质区域的位点特异性切割增加了6至10倍。β-主珠蛋白基因附近的DNase I超敏位点定位于该基因5′端附近的一个小区域。在HMBA介导的红系分化过程中,未观察到α或β珠蛋白基因周围DNA甲基化模式的可检测变化。在β主要珠蛋白基因附近测定和定位的潜在甲基化位点中,在未诱导和诱导细胞中,一个位点完全甲基化,一个位点部分甲基化,一个位点未甲基化。在未诱导和诱导的细胞中,α-珠蛋白基因附近的许多(但不是所有)位点都是未甲基化的。这些结果表明,特定的染色质结构的改变发生在MELC分化,并表明这些变化可能不涉及DNA甲基化模式的改变。
The sensitivity to digestion by DNase I of chromatin containing the α- and βmajor-globin genes and the pattern of DNA methylation near these genes was examined during hexamethylenebisacetamide (HMBA)-mediated erythroid differentiation of murine erythroleukemia cells (MELC). In uninduced and induced cells, the chromatin regions containing the α- and β-major-globin genes are more sensitive to digestion by DNase I than is the region containing an immunoglobulin gene (Igα) not expressed during erythroid differentiation. However, at low concentrations of DNase I, a 6- to 10-fold increase in site-specific cleavages was generated in chromatin regions near both the α- and βmajor-globin genes in cells induced to differentiate by HMBA. The DNase I hypersensitive site near the βmajor-globin gene maps to a small region near the 5′ terminus of the gene. No detectable change in the pattern of DNA methylation around either the α- or β-globin genes was observed during HMBA-mediated erythroid differentiation. Of the potentially methylated sites assayed and mapped near the βmajor-globin gene, one site is fully methylated, one is partially methylated, and one is unmethylated both in uninduced and induced cells. Many (but not all) sites assayed near the α-globin genes are unmethylated in both uninduced and induced cells. These results show that specific alterations of chromatin structure occur during MELC differentiation and suggest that these changes may not involve alterations in the pattern of DNA methylation.