Howe Françoise S, Mellor Jane
Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
Microb Cell. 2014 Jan 23;1(11):390-392. doi: 10.15698/mic2014.11.176.
Acetylation of lysine residues has several characterised functions in chromatin. These include neutralization of the lysine's positive charge to directly influence histone tail-DNA/internucleosomal interactions or indirect effects via bromodomain-containing effector proteins. Recently, we described a novel function of lysine acetylation to influence proline isomerization and thus local protein conformation. We found that acetylation of lysine 14 in the histone H3 N-terminal tail (H3K14ac), an intrinsically disordered domain, increased the proportion of neighbouring proline 16 (H3P16) in the conformation. This conformation of the tail was associated with reduced tri-methylation on histone H3 lysine 4 (H3K4me3) due to both decreased methylation by the Set1 methyltransferase (with the me3-specific subunit Spp1) and increased demethylation by the demethylase Jhd2. Interestingly, H3K4me3 on individual genes was differentially affected by substitution of H3K14 or H3P16, with ribosomal protein genes losing the least H3K4me3 and environmental stress-induced genes losing the most.
赖氨酸残基的乙酰化在染色质中具有多种已明确的功能。这些功能包括中和赖氨酸的正电荷，以直接影响组蛋白尾部与DNA/核小体间的相互作用，或通过含溴结构域的效应蛋白产生间接影响。最近，我们描述了赖氨酸乙酰化的一种新功能，即影响脯氨酸异构化，进而影响局部蛋白质构象。我们发现，组蛋白H3 N端尾部（H3K14ac）中赖氨酸14的乙酰化（这是一个内在无序结构域）增加了相邻脯氨酸16（H3P16）处于顺式构象的比例。尾部的这种构象与组蛋白H3赖氨酸4（H3K4me3）的三甲基化减少有关，这是由于Set1甲基转移酶（与me3特异性亚基Spp1一起）的甲基化作用降低以及去甲基化酶Jhd2的去甲基化作用增强所致。有趣的是，单个基因上的H3K4me3受H3K14或H3P16取代的影响存在差异，核糖体蛋白基因失去的H3K4me3最少，而环境应激诱导基因失去的最多。
