Cigarette Smoke Component Acrolein Modulates Chromatin Assembly by Inhibiting Histone Acetylation
Cigarette Smoke Component Acrolein Modulates Chromatin Assembly by Inhibiting Histone Acetylation
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DOI：
10.1074/jbc.m113.476630
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发表时间：
2013-07-26
影响因子：
4.8
通讯作者：
Jin, Chunyuan
中科院分区：
文献类型：
--
作者：
Chen, Danqi;Fang, Lei;Jin, Chunyuan
核小体的组装对染色质结构和基因表达都有调节作用。环境因素如何影响组蛋白核输入和核小体组装途径，导致染色质组织和转录的变化，仍然是未知的。丙烯醛（Acr）是一种α-不饱和醛，在环境中尤其是香烟烟气中含量丰富.它最近被认为是与吸烟有关的肺癌的潜在主要致癌物。在这里，我们表明，Acr形成加合物与组蛋白在体外和体内，并优先与游离组蛋白，而不是与核小体组蛋白反应。细胞分级分析表明，Acr曝光特异性抑制乙酰化的N-末端尾的胞质组蛋白H3和H4，修改是重要的核输入和染色质组装。值得注意的是，Acr暴露损害组蛋白H3向染色质中的递送并增加染色质可及性。此外，在几个基因组位点的核小体占有率的变化与转录反应Acr曝光。我们的数据为环境因素与基因组相互作用并影响基因组功能的机制提供了新的见解。
Chromatin structure and gene expression are both regulated by nucleosome assembly. How environmental factors influence histone nuclear import and the nucleosome assembly pathway, leading to changes in chromatin organization and transcription, remains unknown. Acrolein (Acr) is an ,-unsaturated aldehyde, which is abundant in the environment, especially in cigarette smoke. It has recently been implicated as a potential major carcinogen of smoking-related lung cancer. Here we show that Acr forms adducts with histone proteins in vitro and in vivo and preferentially reacts with free histones rather than with nucleosomal histones. Cellular fractionation analyses reveal that Acr exposure specifically inhibits acetylations of N-terminal tails of cytosolic histones H3 and H4, modifications that are important for nuclear import and chromatin assembly. Notably, Acr exposure compromises the delivery of histone H3 into chromatin and increases chromatin accessibility. Moreover, changes in nucleosome occupancy at several genomic loci are correlated with transcriptional responses to Acr exposure. Our data provide new insights into mechanisms whereby environmental factors interact with the genome and influence genome function.