着丝粒身份由与含有CENP-A靶向结构域的组蛋白H3组装而成的核小体维持。

Centromere identity maintained by nucleosomes assembled with histone H3 containing the CENP-A targeting domain.

作者信息

Black Ben E, Jansen Lars E T, Maddox Paul S, Foltz Daniel R, Desai Arshad B, Shah Jagesh V, Cleveland Don W

机构信息

Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA.

出版信息

Mol Cell. 2007 Jan 26;25(2):309-22. doi: 10.1016/j.molcel.2006.12.018.

DOI:10.1016/j.molcel.2006.12.018

PMID:17244537

Abstract

Active centromeres are marked by nucleosomes assembled with CENP-A, a centromere-specific histone H3 variant. The CENP-A centromere targeting domain (CATD), comprised of loop 1 and the alpha2 helix within the histone fold, is sufficient to target histone H3 to centromeres and to generate the same conformational rigidity to the initial subnucleosomal heterotetramer with histone H4 as does CENP-A. We now show in human cells and in yeast that depletion of CENP-A is lethal, but recruitment of normal levels of kinetochore proteins, centromere-generated mitotic checkpoint signaling, chromosome segregation, and viability can be rescued by histone H3 carrying the CATD. These data offer direct support for centromere identity maintained by a unique nucleosome that serves to distinguish the centromere from the rest of the chromosome.

摘要

活性着丝粒由与CENP-A组装的核小体标记，CENP-A是一种着丝粒特异性组蛋白H3变体。CENP-A着丝粒靶向结构域（CATD）由组蛋白折叠中的环1和α2螺旋组成，足以将组蛋白H3靶向着丝粒，并与CENP-A一样，为初始亚核小体异源四聚体与组蛋白H4产生相同的构象刚性。我们现在在人类细胞和酵母中表明，CENP-A的缺失是致命的，但携带CATD的组蛋白H3可以挽救正常水平的动粒蛋白募集、着丝粒产生的有丝分裂检查点信号、染色体分离和细胞活力。这些数据为通过独特核小体维持的着丝粒身份提供了直接支持，该核小体用于将着丝粒与染色体的其余部分区分开来。