The chromatin remodeler RSC prevents ectopic CENP-A propagation into pericentromeric heterochromatin at the chromatin boundary

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-A(Cnp1) 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-A(Cnp1) from spreading into neighbouring heterochromatin, where deacetylated histones provide an ideal environment for the spread of CENP-A(Cnp1). 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-A(Cnp1) into pericentromeric heterochromatin. Our study provides an insight into how the distribution of distinct chromatin domains is established and maintained.

Automated summary

This study reveals the crucial role of chromatin remodeler RSC in the establishment and maintenance of distinct chromatin domains, particularly centromeres, in eukaryotic cells. RSC prevents the spreading of CENP-A(Cnp1) into heterochromatin and controls its distribution by decompacting the chromatin structure.