Structural and Functional Dynamics of Human Centromeric Chromatin

Abstract

Centromeres are the elements of chromosomes that assemble the proteinaceous kinetochore, maintain sister chromatid cohesion, regulate chromosome attachment to the spindle, and direct chromosome movement during cell division. Although the functions of centromeres and the proteins that contribute to their complex structure and function are conserved in eukaryotes, centromeric DNA diverges rapidly. Human centromeres are particularly complicated. Here, we review studies on the organization of homogeneous arrays of chromosome-specific alpha-satellite repeats and evolutionary links among eukaryotic centromeric sequences. We also discuss epigenetic mechanisms of centromere identity that confer structural and functional features of the centromere through DNA-protein interactions and post-translational modifications, producing centromere-specific chromatin signatures. The assembly and organization of human centromeres, the contributions of satellite DNA to centromere identity and diversity, and the mechanism whereby centromeres are distinguished from the rest of the genome reflect ongoing puzzles in chromosome biology.

Epigenetic engineering: histone H3K9 acetylation is compatible with kinetochore structure and function

“…In humans, endogenous centromeres typically form on chromosome-specific higher-order 'alphoid' DNA arrays, which are composed of 171 bp alpha-satellite monomer units that are tandemly arranged in a directional head-to-tail fashion (Choo et al, 1991;Mitchell et al, 1985;Schueler and Sullivan, 2006;Willard and Waye, 1987). Independent of this sequence preference, specific deposition of the centromeric histone H3 variant CENP-A (Earnshaw and Rothfield, 1985) is thought to form the basis for an 'epigenetic' maintenance of centromere identity (Allshire and Karpen, 2008;Okamoto et al, 2007;Vafa and Sullivan, 1997;Warburton et al, 1997).…”

Human gamma-satellite DNA maintains open chromatin structure and protects a transgene from epigenetic silencing

“…The major mouse satellite is found in the pericentromeric region, and the minor mouse satellite is found in the centric constriction of the centromere (Choo 1997;Schueler and Sullivan 2006).…”

“…One hallmark of all functional centromeres is the presence of the H3 variant, CENP-A (Sullivan and Karpen 2004;Lam et al 2006;Schueler and Sullivan 2006). CENP-A is associated with the centromere/ kinetochore, the large protein/DNA complex that attaches to spindle microtubes during mitosis and that includes highly homogeneous alpha-satellite DNA in human and minor satellite DNA in mouse.…”

Principles and practice of nucleosome positioningin vitro

“…Alpha satellite DNA is a 171 bp conserved repeat found at the core centromere of primates (Schueler and Sullivan 2006). Distributed copies of the repeat contain a 17 bp site for the sequence-specific, non-essential CENP-B binding protein.…”