Centromeres are the chromosomal domains that specify the mitotic behavior of chromosomes. The CENPA gene encodes a centromere protein which contains a histone H3 related histone fold domain that is required for targeting to the centromere. CENPA is proposed to be a component of a modified nucleosome or nucleosome-like structure in which it replaces 1 or both copies of conventional histone H3 in the (H3-H4)2 tetrameric core of the nucleosome particle. Alternative splicing results in multiple transcript variants encoding distinct isoforms.
In higher eukaryotes, the recruitment of CENP-A nucleosomes to existing centromeres is an epigenetic process, independent of the underlying DNA sequence. In S.pombe, de novo recruitment of the CENP-A to the centromere is believed to be controlled by "centromeric" heterochromatin surrounding the centromere, and by an RNAi mechanism. The RNAi is cut to form siRNA; this complexes with the protein Chp1, which then binds the centromeric heterochromatin. This helps recruit other proteins, ultimately resulting in a protein complex that forms cohesin between two sister chromatids at the centromeric heterochromatin. This cohesin is believed to be essential in replacing the centromere H3 with CENP-A. CENP-A is one of the epigenetic changes that is believed to distinguish centromeric DNA from other DNA. Once the CENP-A has been added, the centromere becomes self-propagating, and the surrounding heterochromatin/RNAi mechanism is no longer necessary.
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