Chromatin proteins are determinants of centromere function

Abstract

Recent advances in the identification of molecular components of centromeres have demonstrated a crucial role for chromatin proteins in determining both centromere identity and the stability of kinetochore-microtubule attachments. Although we are far from a complete understanding of the establishment and propagation of centromeres, this review seeks to highlight the contribution of histones, histone deposition factors, histone modifying enzymes, and heterochromatin proteins to the assembly of this sophisticated, highly specialized chromatin structure. First, an overview of DNA sequence elements at centromeric regions will be presented. We will then discuss the contribution of chromatin to kinetochore function in budding yeast, and pericentric heterochromatin domains in other eukaryotic systems. We will conclude with discussion of specialized nucleosomes that direct kinetochore assembly and propagation of centromere-defining chromatin domains.

Figure 1

Consensus centromere in S. cerevisiae (after Hegeman and Fleig, 1993). Sequence elements present at all sixteen chromosomes are denoted CDEI, CDEII, and CDEIII. Invariant residues of the CDEI and CDEIII elements are marked in bold.

Figure 2

Consensus centromere in S. pombe. The core centromere is flanked by imr and otr repeat sequence elements. See text for details.

Figure 3

Chromatin domains at S. cerevisiae centromeres. Kinetochore proteins localize to the conserved core seqence, some have been omitted for clarity. Kinetochore regions are flanked by highly positioned nucleosomes that extend outward along chromosome arms. The CAF-I and cohesin protein complexes pictured above the diagram indicate widespread association across the entire CEN region (Blat and Kleckner 1999; Megee et al. 1999; Tanaka et al. 1999; Sharp et al. 2002). The Hir1 protein has been localized to centromeres by indirect immunofluorescence (Sharp et al., 2002).

Figure 4

Chromatin domains at S. pombe centromeres. The core centromere is occupied by specialized Cnp-1 (CENP-A homolog) containing nucleosomes and kinetochore proteins. A tRNA gene (stippled boxes) marks a transition zone betweeen the core-associated proteins and the heterochromatic outer repeats. Swi6 (HP1 homolog) and Chp1-associated regions of centric heterochromatin define a zone of strong transcriptional silencing and nuclease-resistant chromatin. Clr4 (Su(var)3–9 homolog) and Rik1 are required for histone H3 Lys 9 methylation (Nakayama et al. 2001).