Xenopus laevis M18BP1 Directly Binds Existing CENP-A Nucleosomes to Promote Centromeric Chromatin Assembly

Publication date: 24 July 2017
Source:Developmental Cell, Volume 42, Issue 2
Author(s): Bradley T. French, Frederick G. Westhorpe, Charles Limouse, Aaron F. Straight
Vertebrate centromeres are epigenetically defined by nucleosomes containing the histone H3 variant, CENP-A. CENP-A nucleosome assembly requires the three-protein Mis18 complex (Mis18α, Mis18β, and M18BP1) that recruits the CENP-A chaperone HJURP to centromeres, but how the Mis18 complex recognizes centromeric chromatin is unknown. Using Xenopus egg extract, we show that direct, cell-cycle-regulated binding of M18BP1 to CENP-A nucleosomes recruits the Mis18 complex to interphase centromeres to promote new CENP-A nucleosome assembly. We demonstrate that Xenopus M18BP1 binds CENP-A nucleosomes using a motif that is widely conserved except in mammals. The M18BP1 motif resembles a CENP-A nucleosome binding motif in CENP-C, and we show that CENP-C competes with M18BP1 for CENP-A nucleosome binding at centromeres. We show that both CENP-C and M18BP1 recruit HJURP to centromeres for new CENP-A assembly. This study defines cellular mechanisms for recruiting CENP-A assembly factors to existing CENP-A nucleosomes for the epigenetic inheritance of centromeres.

Teaser

Centromeres are assembled upon nucleosomes containing the histone H3 variant, CENP-A, but how new CENP-A is assembled at centromeres following DNA replication is unclear. French et al. show that M18BP1 directly binds CENP-A nucleosomes and promotes local CENP-A assembly to maintain centromeres through each cell division.


http://ift.tt/2vVByUY