Epigenetic regulation of centromeric chromatin: old dogs, new tricks?

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Abstract
Chromosomal DNA is packaged with histones into nucleosomes. Following replication, sister-chromatid segregation is orchestrated to ensure that each daughter cell receives a complete set of chromosomes. The centromere is the chromosomal region responsible for formation of the kinetochore, which mediates attachment to spindle microtubules and chromosome movement. In organisms with complex centromeres the site of kinetochore assembly is epigenetically determined and is not strictly governed by primary DNA sequence. The key determining factor in specifying the site of kinetochore assembly is the deposition of the centromere-specific histone H3 variant CENP-A. In tissue-culture cells, new CENP-A is deposited during late mitosis and through G1, independently of DNA replication. A portion of the histone fold domain of CENP-A is necessary and sufficient for targeting to centromeres. CENP-A nucleosomes depleted during S phase replication are restored later in the cell cycle by de novo deposition into 'gaps' or by replacement of H3 nucleosomes. Numerous factors have been identified that are required for CENP-A localization, but the chromatin assembly proteins that are directly required for propagation of CENP-A chromatin are not known. Non-coding transcripts and transcription factors are associated with centromeres, and transcription might be linked to CENP-A chromatin assembly in some systems. CENP-B binding sites and flanking centric heterochromatin influence the establishment of CENP-A chromatin on naive templates.