Remarkable Evolutionary Plasticity of Centromeric Chromatin

Abstract

Centromeres were familiar to cell biologists in the late 19th century, but for most eukaryotes the basis for centromere specification has remained enigmatic. Much attention has been focused on the cenH3 (CENP-A) histone variant, which forms the foundation of the centromere. To investigate the DNA sequence requirements for centromere specification, we applied a variety of epigenomic approaches, which have revealed surprising diversity in centromeric chromatin properties. Whereas each point centromere of budding yeast is occupied by a single precisely positioned tetrameric nucleosome with one cenH3 molecule, the "regional" centromeres of fission yeast contain unphased presumably octameric nucleosomes with two cenH3s. In Caenorhabditis elegans, kinetochores assemble all along the chromosome at sites of cenH3 nucleosomes that resemble budding yeast point centromeres, whereas holocentric insects lack cenH3 entirely. The "satellite" centromeres of most animals and plants consist of cenH3-containing particles that are precisely positioned over homogeneous tandem repeats, but in humans, different α-satellite subfamilies are occupied by CENP-A nucleosomes with very different conformations. We suggest that this extraordinary evolutionary diversity of centromeric chromatin architectures can be understood in terms of the simplicity of the task of equal chromosome segregation that is continually subverted by selfish DNA sequences.

i-Motif DNA: structural features and significance to cell biology

“…However, the possible role of the centromeric DNA sequences in directing the formation of such specialized chromatin has been suggested and is an attractive matter of debate ( 99 , 100 ). Interestingly, Kasinathan and Henikoff proposed in a very recent report that the predominant formation of non-B DNA structures in centromeric DNA sequences might be the basis for the constitution of centromeric chromatin ( 101 ).…”

“…The presence of the above mentioned i-motif forming sequences at the entrance and exit of the nucleosome would facilitate their participation in dimeric i-motifs formation (Figure 6C ). Thus, not only non-B DNA structures may have a role in directing centromere location ( 101 ) but also in providing particular architectural features to the centromere.…”

Sequence, Chromatin and Evolution of Satellite DNA

“…Although centromeric DNA sequences are not evolutionarily conserved, most eukaryotic lineages assemble nucleosomes in which histone H3 is replaced by its (cenH3) variant, Centromeric protein A (CENP-A) [ 194 , 195 , 196 ]. CENP-A nucleosomes serve as the chromatin foundation for the kinetochore, an assemblage of multi-protein complexes that make direct connections with growing and shrinking spindle microtubules to mediate chromosome segregation [ 197 , 198 ].…”

CenH3 distribution reveals extended centromeres in the model beetle Tribolium castaneum

“…In the absence of a DNA cornerstone, the currently accepted definition of centromere identity is formulated epigenetically and relies on the presence of CenH3 proteins, centromere-specific histone H3 variants [ 11 ]. The human CENP-A was the first detected CenH3 protein [ 12 ], and afterwards its homologues have been identified in a wide range of eukaryotic organisms, from yeast to different animal and plant species [ 13 ]. Unlike the canonical histone H3, that is evolutionary well-conserved across eukaryotes, CenH3 proteins show considerable sequence variability at different taxonomic levels.…”