M18BP1 valency and a distributed interaction footprint determine epigenetic centromere specification in humans

ABSTRACT: The histone H3 variant CENP-A is considered an epigenetic landmark of centromeres. Its deposition reflects cell-cycle-regulated assembly of M18BP1, HJURP, and PLK1 on a divalent MIS18α/β scaffold. The localization determinants of this machinery remain poorly characterized. Here we report that in human cells, artificial M18BP1 dimerization bypasses MIS18α/β, allowing the identification of at least four determinants of M18BP1 centromere localization. These include the SANTA domain, of which we report the first structure, as well as linear motifs in disordered neighboring regions, of which we characterize the interaction footprint on the CENP-A associated 16-subunit constitutive centromere-associated network (CCAN). Our observations imply that M18BP1, after dimerization, is necessary and suff

SUBMITTER: Kai Walstein 

PROVIDER: S-SCDT-10_1038-S44318-026-00698-Z | biostudies-other |

REPOSITORIES: biostudies-other