An Epigenetic Mark Generated by the Incorporation of CENP-A into Centromeric Nucleosomes

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2007 Mar 16

PMID 17360341

Citations 90

Authors

Ben E Black

Melissa A Brock

Sabrina Bedard

Virgil L Woods Jr

Don W Cleveland

Affiliations

Soon will be listed here.

Abstract

Mammalian centromeres are defined epigenetically. Although the physical nature of the epigenetic mark is unknown, nucleosomes in which CENP-A replaces histone H3 are at the foundation of centromeric chromatin. Hydrogen/deuterium exchange MS is now used to show that assembly into nucleosomes imposes stringent conformational constraints, reducing solvent accessibility in almost all histone regions by >3 orders of magnitude. Despite this, nucleosomes assembled with CENP-A are substantially more conformationally rigid than those assembled with histone H3 independent of DNA template. Substitution of the CENP-A centromere targeting domain into histone H3 to convert it into a centromere-targeted histone that can functionally replace CENP-A in centromere maintenance generates the same more rigid nucleosome, as does CENP-A. Thus, the targeting information directing CENP-A deposition at the centromere produces a structurally distinct nucleosome, supporting a CENP-A-driven self-assembly mechanism that mediates maintenance of centromere identity.

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