Histone-varianten in het Centromeer

The centromere is a constricted region on each chromosome where the kinetochore and microtubules assemble to ensure faithful separation of the chromatids during anaphase of cell division. 

In most eukaryotes, the centromere is partitioned into two chromatin domains- the centromere core and the pericentric heterochromatin region.

The centromere core in all eukaryotes contains a variant of core histone H3, called Centromere Protein A or CENP-A. Together with the three other core histones H2A, H2B, and H4, the CENP-A forms the centromere-specific nucleosome. 

The functional C-terminal fold domain of the CENP-A is highly conserved among eukaryotes. However, the N-terminal tail of the protein shows significant variations both in size and sequence.

The centromere cores in the yeast Saccharomyces cerevisiae contain a single CENP-A nucleosome attached to a single mitotic spindle; hence, these are referred to as point centromeres. 

This core centromere region is flanked by approximately 125 bps of AT-rich pericentric DNA sequences. This region is characterized by nucleosomes containing methylated histone H3.

The centromere chromatin forms a three-dimensional structure to expose CENP-A containing nucleosomes for interaction with the kinetochore and microtubules. 

In contrast, the centromere core of human chromosomes has alternatively arranged CENP-A nucleosomes and regular H3 nucleosomes. These regular H3 nucleosomes are dimethylated. 

These alternating blocks can span up to 5 Mbs long and largely contain short, repeated AT-rich DNA sequences called alpha satellite DNA, flanked by pericentric heterochromatin DNA.

The timing of CENP-A loading to nucleosomes also differs between species. For example, while in humans, it's loaded between the anaphase and G1 phases; in plants, the loading occurs in the late G2 phase.