Department of Physics, The Ohio State University, Columbus, OH 43210, USA.
Nucleic Acids Res. 2012 Nov 1;40(20):10215-27. doi: 10.1093/nar/gks747. Epub 2012 Sep 10.
Eukaryotic genomes are repetitively wrapped into nucleosomes that then regulate access of transcription and DNA repair complexes to DNA. The mechanisms that regulate extrinsic protein interactions within nucleosomes are unresolved. We demonstrate that modulation of the nucleosome unwrapping rate regulates protein binding within nucleosomes. Histone H3 acetyl-lysine 56 [H3(K56ac)] and DNA sequence within the nucleosome entry-exit region additively influence nucleosomal DNA accessibility by increasing the unwrapping rate without impacting rewrapping. These combined epigenetic and genetic factors influence transcription factor (TF) occupancy within the nucleosome by at least one order of magnitude and enhance nucleosome disassembly by the DNA mismatch repair complex, hMSH2-hMSH6. Our results combined with the observation that ∼30% of Saccharomyces cerevisiae TF-binding sites reside in the nucleosome entry-exit region suggest that modulation of nucleosome unwrapping is a mechanism for regulating transcription and DNA repair.
真核基因组重复包裹在核小体中，然后调节转录和 DNA 修复复合物对 DNA 的访问。调节核小体中外在蛋白质相互作用的机制尚未解决。我们证明，核小体解缠绕速率的调节控制着核小体内部的蛋白质结合。核小体进入-退出区域的组蛋白 H3 乙酰-赖氨酸 56[H3(K56ac)]和 DNA 序列通过增加解缠绕速率而不影响重缠绕来加和性地影响核小体 DNA 的可及性。这些组合的表观遗传和遗传因素通过至少一个数量级影响转录因子 (TF) 在核小体中的占据，并通过 DNA 错配修复复合物 hMSH2-hMSH6 增强核小体的解体。我们的结果结合了这样一个观察结果，即在酿酒酵母中，约 30%的 TF 结合位点位于核小体进入-退出区域，这表明调节核小体解缠绕是调节转录和 DNA 修复的一种机制。
