Molecular characterization of centromeres has been slow because of technical difficulties, not because of any lack of appreciation of the importance of these structures in cell division. Centromeric DNA in complex genomes consists of tandem repeats, which are difficult to clone, amplify or sequence. Centromeric cores are the most uniformly repetitive regions, consisting of megabase-sized, homogeneous arrays of short tandem-repeat units. These are flanked by more heterogeneous repeats, including the descendants of transposable elements — sequences that can insert themselves randomly throughout genomes. The flanking repeats mediate cohesion between sister chromosomes, and simultaneous dissolution of cohesion on all chromosomes defines the beginning of the anaphase of mitosis, when sister chromosomes begin moving to opposite spindle poles.

This functional distinction between the centromere's core, which is where the spindle microtubules attach, and its flanks, which maintain cohesion, mirrors a biochemical distinction. Half of our genetic material by weight is in the form of octamers composed of four histone proteins (H2A, H2B, H3 and H4), around which DNA is wrapped to form nucleosomes, the basic units of chromatin. Centromeric cores consist of nucleosomes with a variant H3 histone (CenH3) that replaces the usual version. Flanking sequences are packaged into 'heterochromatin', which is distinguished from gene-rich 'euchromatin' by the presence of methyl groups attached to lysine at position 9 of H3. Just how differences in H3 specify chromatin function is of substantial current interest.

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