Department of Physiological Chemistry; Butenandt Institute and LMU Biomedical Center, Faculty of Medicine; Ludwig Maximilians University of Munich; Munich, Germany; Munich Cluster for Systems Neurology (SyNergy); Munich, Germany; Center for Integrated Protein Science Munich (CIPSM); Munich, Germany.
Nucleus. 2013 Nov-Dec;4(6):443-9. doi: 10.4161/nucl.27235. Epub 2013 Dec 5.
Nucleosomes confer a barrier to processes that require access to the eukaryotic genome such as transcription, DNA replication and repair. A variety of ATP-dependent nucleosome remodeling machines and ATP-independent histone chaperones facilitate nucleosome dynamics by depositing or evicting histones and unwrapping the DNA. It is clear that remodeling machines can use the energy from ATP to actively destabilize, translocate or disassemble nucleosomes. But how do ATP-independent histone chaperones, which "merely" bind histones, contribute to this process? Using our recent structural analysis of the conserved and essential eukaryotic histone chaperone FACT in complex with histones H2A-H2B as an example, we suggest that FACT capitalizes on transiently exposed surfaces of the nucleosome. By binding these surfaces, FACT stabilizes thermodynamically unfavorable intermediates of the intrinsically dynamic nucleosome particle. This makes the nucleosome permissive to DNA and RNA polymerases, providing temporary access, passage, and read-out.
核小体为需要访问真核生物基因组的过程（如转录、DNA 复制和修复）设置了障碍。各种依赖 ATP 的核小体重塑机器和非依赖 ATP 的组蛋白伴侣通过沉积或驱逐组蛋白以及解开 DNA，促进核小体动力学。显然，重塑机器可以利用 ATP 能量来主动破坏、转位或分解核小体。但是，“仅仅”结合组蛋白的非依赖 ATP 的组蛋白伴侣如何促进这一过程？我们最近对保守且必需的真核组蛋白伴侣 FACT 与 H2A-H2B 组蛋白复合物的结构分析为例，提出 FACT 利用核小体的瞬时暴露表面。通过结合这些表面，FACT 稳定了内在动态核小体颗粒的热力学不利中间体。这使得核小体允许 DNA 和 RNA 聚合酶进入，提供临时的访问、通道和读取。
