Nucleosome Organization Affects the Sensitivity of Gene Expression to Promoter Mutations
Nucleosome Organization Affects the Sensitivity of Gene Expression to Promoter Mutations
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DOI：
10.1016/j.molcel.2012.02.019
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发表时间：
2012-05-11
期刊：
影响因子：
16
通讯作者：
Barkai, Naama
中科院分区：
文献类型：
--
作者：
Hornung, Gil;Oren, Moshe;Barkai, Naama
基因表达在相关物种之间迅速分化，在新表型的进化中起着关键作用。基因之间的分歧程度差异很大，并与启动子核小体组织。我们推测，这可能是部分解释的差异敏感性的表达在启动子区的突变。我们测量了22个酵母启动子与不同的核小体模式序列中的随机突变的敏感性。启动子之间的突变敏感性差异高达10倍。这种差异不能用转录因子结合位点的丰度来解释。相反，突变敏感性与近端启动子区核小体的相对占有率呈正相关。此外，突变敏感性降低后，引入Reb 1，一个因素，阻止核小体形成的结合位点，这表明核小体组织直接调节突变敏感性。我们的研究表明，染色质结构在基因表达的进化中起着重要作用。
Gene expression diverges rapidly between related species, playing a key role in the evolution of new phenotypes. The extent of divergence differs greatly between genes and is correlated to promoter nucleosome organization. We hypothesized that this may be partially explained by differential sensitivity of expression to mutations in the promoter region. We measured the sensitivity of 22 yeast promoters with varying nucleosome patterns to random mutations in sequence. Mutation sensitivity differed by up to 10-fold between promoters. This difference could not be explained by the abundance of transcription factor binding sites. Rather, mutation sensitivity positively correlated with the relative occupancy of nucleosomes at the proximal promoter region. Furthermore, mutation sensitivity was reduced upon introduction of a binding site for Reb1, a factor that blocks nucleosome formation, suggesting that nucleosome organization directly regulates mutation sensitivity. Our study suggests an important role for chromatin structure in the evolution of gene expression.