Sodium butyrate induces new gene expression in Friend erythroleukemic cells.
Sodium butyrate induces new gene expression in Friend erythroleukemic cells.
复制标题
丁酸钠在 Friend 红白血病细胞中诱导新基因表达。
DOI：
10.1016/s0021-9258(18)50727-4
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发表时间：
1979
期刊：
影响因子：
--
通讯作者：
P. Cserjesi
中科院分区：
文献类型：
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作者：
R. Reeves;P. Cserjesi
用毫摩尔浓度的n-Bu-@rate处理Friend红白血病细胞24小时后，染色质组蛋白(特别是核小体核心组蛋白H3和H4)已过度乙酰化。在同一时间段，核酸杂交研究表明，丁酸处理的Friend细胞积累了大约38%的新RNA转录本，这些转录本是由独特的小鼠DNA序列合成的。这些丁酸诱导的RNA转录本在对照、非脂肪酸处理的细胞中检测不到。此外，丁酸处理的细胞的双向凝胶电泳分析还表明，脂肪酸诱导的细胞合成了许多在对照细胞中检测不到的新蛋白质。当向Friend细胞中加入其他明显的红系分化诱导剂，如二甲基亚砜(不会导致组蛋白超乙酰化)时，RNA和蛋白质合成的这些新的变化不会发生。最后，一旦脂肪酸被去除，丁酸盐短期处理细胞所产生的所有这些代谢影响都很容易逆转。丁酸在诱导组蛋白高乙酰化、诱导新的独特序列基因RNA转录积累和诱导新的蛋白质合成方面的显著协同作用表明，在Friend红白血病细胞中，这三种代谢现象可能是密切相关的。此外，这些发现与以下假设并不矛盾，即组蛋白超乙酰化(特别是H3和H4转变为双乙酰化和更高修饰形式)可能是导致这些细胞中新基因组表达的生化机制的必要的，但显然不是充分的。在许多有文献记载的毫摩尔浓度的丁酸钠对组织培养中生长的哺乳动物细胞的影响中，包括诱导在基本染色质亚基-核小体中发现的大多数组蛋白的超乙酰化(L-3)。例如，在丁酸盐处理后的许多不同类型的脊椎动物细胞中，超过80%的组蛋白H4被转化为单、双、三和四乙酰化形式(L-5)。此外，在所有这些细胞类型中，组蛋白H3也变得过度乙酰化，某些大鼠组织培养细胞系中的组蛋白H_2A和H_2B也是如此(1)。这些修饰的组蛋白实际上存在于染色质中
Twenty-four hours after treatment of Friend erythroleukemic cells with millimolar concentrations of n-bu-@ rate, the chromatin histones (particularly the nucleosome core histones H3 and H4) have become hyperacetylated. During this same time period, nucleic acid hybridization studies indicate that the butyrate-treated Friend cells accumulate a population of about 38% new RNA transcripts synthesized from unique sequences of mouse DNA. These butyrate-induced RNA transcripts are not detectable in control, non-fatty acid-treated cells. Furthermore, two-dimensional gel electrophoretie analysis of the butyrate-treated cells also indicates that the fatty acid-induced cells synthesize many new species of proteins that are not detectable in the control cells. These de nouo changes in RNA and protein synthesis do not occur when other inducers of overt erythroid differentiation, such as dimethyl sulfoxide (which does not lead to histone hyperacetylation), are added to the Friend cells. Finally, all of these metabolic effects of short term treatment of cells with butyrate are readily reversible once the fatty acid is removed. This remarkable coordinate effect of butyrate on the induction of histone hyperacetylation, the induction of new unique sequence gene RNA transcript accumulation, and the induction of new protein synthesis suggests that these three metabolic phenomena may be closely linked in Friend erythroleukemic cells. Furthermore, these findings are not inconsistent with the hypothesis that histone hyperacetylation(especially of H3 and H4 to the diacetylated and higher modified forms) may be a necessary, but obviously not sufficient, part of the biochemical mechanisms leading to new genomic expression in these cells.Among the many documented effects of millimolar concentrations of sodium butyrate on mammalian cells growing in tissue culture is the induction of hyperacetylation of most of the histones found in the fundamental chromatin subunit, the nucleosome (l-3). For example, over 80% of histone H4 is converted to the mono-, di-, tri-, and tetraacetylated forms in a number of different types of cultured vertebrate cells after butyrate treatment (l-5). Furthermore, in all of these cell types, histone H3 also becomes hyperacetylated as do histones H2A and H2B in certain rat tissue culture cell lines (1). That these modified histones are actually present in chromatin