Falk Samantha J, Guo Lucie Y, Sekulic Nikolina, Smoak Evan M, Mani Tomoyasu, Logsdon Glennis A, Gupta Kushol, Jansen Lars E T, Van Duyne Gregory D, Vinogradov Sergei A, Lampson Michael A, Black Ben E
Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Graduate Program in Cell and Molecular Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Graduate Program in Biochemistry and Molecular Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Science. 2015 May 8;348(6235):699-703. doi: 10.1126/science.1259308.
Inheritance of each chromosome depends upon its centromere. A histone H3 variant, centromere protein A (CENP-A), is essential for epigenetically marking centromere location. We find that CENP-A is quantitatively retained at the centromere upon which it is initially assembled. CENP-C binds to CENP-A nucleosomes and is a prime candidate to stabilize centromeric chromatin. Using purified components, we find that CENP-C reshapes the octameric histone core of CENP-A nucleosomes, rigidifies both surface and internal nucleosome structure, and modulates terminal DNA to match the loose wrap that is found on native CENP-A nucleosomes at functional human centromeres. Thus, CENP-C affects nucleosome shape and dynamics in a manner analogous to allosteric regulation of enzymes. CENP-C depletion leads to rapid removal of CENP-A from centromeres, indicating their collaboration in maintaining centromere identity.
每条染色体的遗传取决于其着丝粒。一种组蛋白H3变体,即着丝粒蛋白A(CENP - A),对于在表观遗传上标记着丝粒位置至关重要。我们发现CENP - A在其最初组装的着丝粒上被定量保留。CENP - C与CENP - A核小体结合,是稳定着丝粒染色质的主要候选蛋白。使用纯化的成分,我们发现CENP - C重塑了CENP - A核小体的八聚体组蛋白核心,使核小体表面和内部结构变硬,并调节末端DNA以匹配在功能性人类着丝粒的天然CENP - A核小体上发现的松散缠绕。因此,CENP - C以类似于酶的别构调节的方式影响核小体的形状和动力学。CENP - C的缺失导致CENP - A从着丝粒快速去除,表明它们在维持着丝粒身份方面的协作。