Laboratory of Bioorganic Chemistry, Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan.
Laboratory of Cell Regulation, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan.
Nucleic Acids Res. 2022 Oct 28;50(19):10914-10928. doi: 10.1093/nar/gkac827.
Centromeres of most eukaryotes consist of two distinct chromatin domains: a kinetochore domain, identified by the histone H3 variant, CENP-A, and a heterochromatic domain. How these two domains are separated is unclear. Here, we show that, in Schizosaccharomyces pombe, mutation of the chromatin remodeler RSC induced CENP-ACnp1 misloading at pericentromeric heterochromatin, resulting in the mis-assembly of kinetochore proteins and a defect in chromosome segregation. We find that RSC functions at the kinetochore boundary to prevent CENP-ACnp1 from spreading into neighbouring heterochromatin, where deacetylated histones provide an ideal environment for the spread of CENP-ACnp1. In addition, we show that RSC decompacts the chromatin structure at this boundary, and propose that this RSC-directed chromatin decompaction prevents mis-propagation of CENP-ACnp1 into pericentromeric heterochromatin. Our study provides an insight into how the distribution of distinct chromatin domains is established and maintained.
一个动粒结构域，由组蛋白 H3 变体 CENP-A 识别，和一个异染色质结构域。这两个结构域是如何分开的尚不清楚。在这里，我们表明，在裂殖酵母中，染色质重塑因子 RSC 的突变会导致 CENP-ACnp1 在着丝粒周围异染色质上的错误加载，从而导致动粒蛋白的错误组装和染色体分离缺陷。我们发现 RSC 在动粒边界发挥作用，以防止 CENP-ACnp1 扩散到相邻的异染色质中，而去乙酰化的组蛋白为 CENP-ACnp1 的扩散提供了理想的环境。此外，我们还表明，RSC 使这个边界处的染色质结构解压缩，并提出这种 RSC 指导的染色质解压缩可以防止 CENP-ACnp1 错误地扩散到着丝粒周围的异染色质中。我们的研究提供了一个深入了解如何建立和维持不同染色质结构域分布的视角。
