Butyrate suppression of histone deacetylation leads to accumulation of multiacetylated forms of histones H3 and H4 and increased DNase I sensitivity of the associated DNA sequences.
Butyrate suppression of histone deacetylation leads to accumulation of multiacetylated forms of histones H3 and H4 and increased DNase I sensitivity of the associated DNA sequences.
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DOI：
10.1073/pnas.75.5.2239
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发表时间：
1978-05
影响因子：
11.1
通讯作者：
G. Vidali;L. Boffa;E. Bradbury;V. Allfrey
中科院分区：
文献类型：
--
作者：
G. Vidali;L. Boffa;E. Bradbury;V. Allfrey
将HeLa细胞暴露于丁酸钠会导致组蛋白H3和H4的多乙酰化形式积累。我们在HeLa S-3细胞中组蛋白乙酰化的研究表明，7 mM丁酸盐抑制组蛋白的去乙酰化，而不影响放射性醋酸酯的掺入速率。在高度乙酰化的染色质中，核小体结构的变化表现为DNA被DNase I降解的速度加快。乙酰化组蛋白与DNase I敏感序列的密切联系得到了证实，有限的DNase I消化后剩余的组蛋白被耗尽为多乙酰化形式的组蛋白H3和H4。DNase I处理也被发现在先前被证明优先降解甲状旁腺细胞染色质中的Globlin基因的条件下，选择性地从鸟类红细胞核中释放[~3H]乙酰标记的H3和H4。我们的结果与这样的观点是一致的，即组蛋白乙酰化提供了在核小体水平改变染色质结构的机制的关键，这可能解释了不同细胞类型中转录活性DNA序列对DNase I的选择性敏感性。
Exposure of HeLa cells to Na butyrate leads to an accumulation of multiacetylated forms of histones H3 and H4. Our studies of histone acetylation in HeLa S-3 cells show that 7 mM butyrate suppresses the deacetylation of histones without influencing the rate of radioactive acetate incorporation. An alteration in nucleosome structure in highly acetylated chromatin is indicated by an increased rate of DNA degradation by DNase I. A close association of acetylated histones with the DNase I-sensitive sequences is confirmed by the finding that histones remaining after limited DNase I digestion are depleted in the multiacetylated forms of histones H3 and H4. DNase I treatment has also been found to selectively release [3H]acetyl-labeled H3 and H4 from avian erythrocyte nuclei under conditions previously shown to preferentially degrade the globlin genes in erthyrocyte chromatin. Our results are consistent with the view that histone acetylation provides a key to the mechanism for altering chromatin structure at the nucleosomal level, and that this may explain the selective DNase I sensitivity of transcriptionally active DNA sequences in different cell types.