ACETYLATION + METHYLATION OF HISTONES + THEIR POSSIBLE ROLE IN REGULATION OF RNA SYNTHESIS
ACETYLATION + METHYLATION OF HISTONES + THEIR POSSIBLE ROLE IN REGULATION OF RNA SYNTHESIS
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DOI：
10.1073/pnas.51.5.786
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发表时间：
1964-01-01
影响因子：
11.1
通讯作者：
MIRSKY, AE
中科院分区：
文献类型：
--
作者：
ALLFREY, VG;FAULKNER, R;MIRSKY, AE
将要描述的实验涉及组蛋白在核功能中的作用，特别强调通过引入乙酰基和甲基来修饰组蛋白结构的生物合成反应。这些反应已在离体小牛胸腺细胞核中进行了研究，用乙酸-2-C14和甲硫氨酸-甲基-C '4（见参考文献1）作为前体，比较它们与C14-赖氨酸和其他氨基酸的掺入，并测试了嘌呤霉素对不同组蛋白组分合成的影响。我们将提出证据表明，在细胞核中，组蛋白的乙酰化和甲基化很可能发生在多肽链完成之后。这种组蛋白结构的改变，特别是乙酰化，可能影响组蛋白抑制体内核糖核酸合成的能力。这一观点得到了以下发现的支持：当分离的富含精氨酸的组蛋白进行有限的乙酰化时，它们作为小牛胸腺细胞核或大肠杆菌的DNA依赖性RNA聚合酶的RNA合成抑制剂的有效性大部分丧失。然而，这些修饰的组蛋白仍然是强碱性蛋白，它们对DNA的亲和力与它们所来源的母体组蛋白相当。这些发现提出了这样一种可能性，即组蛋白对核RNA代谢的影响可能不仅仅是简单地抑制RNA合成，而且可能存在更微妙的机制，允许在染色体沿着的不同位点抑制和重新激活RNA的产生。在过去的几年里，随着越来越多的实验证据支持组蛋白的作用是抑制染色体的作用，
The experiments to be described are concerned with the role of histones in nuclear function, with particular emphasis on biosynthetic reactions which modify the structure of histones by the introduction of acetyl and methyl groups. These reactions have been studied in isolated calf thymus nucleiin vitro, using acetate-2-C14 and methionine-methyl-C'4 (see ref. 1) as precursors, comparing their incorporation with that of C14-lysine and other amino acids, and testing the effects of Puro-mycinon thesynthesisof different histone fractions. Evidence will be presented to show that, in the cell nucleus, the acetylation and methylation ofthe histones occur very probably after completion of the polypeptide chain. Such modifications of histone structure, acetylation in particular, may affect the capacity of the histonesto inhibit ribonucleic acid synthesis in vivo. This view is supported by the finding that, when isolated arginine-rich histones are subjected to a limited acetylation, they lose much of their effectiveness as inhibitors of RNA synthesis by the DNA-dependent RNA polymerases of calf thymus nuclei or Escherichia coli. Yet, such modified histones are still strongly basic proteins which retain an affinity for DNA comparable to that of the parent histone from which they were derived.The findings introduce the possibility that histone effects on nuclear RNA me-tabolism may involve more than a simpleinhibition of RNA synthesis, and that more subtle mechanisms may exist which permit both inhibition and reactivation of RNA production at different loci along the chromosome. Interest in the histones as regulators of chromosomal activity has heightened considerably in the past few years, as increasing experimental evidence has ac-cumulated to support the view that the role of histones is to inhibit chromosomal