The Human Inner Kinetochore Associates with Structurally Distinct CENP-A Nucleosomes

Authors

• DP Melters
• S Gregoryev
• Y Dalal

Abstract

The centromere is a vital locus on each chromosome which seeds the kinetochore, allowing for a physical connection between the chromosome and the mitotic spindle. At the heart of the centromere is the centromere-specific histone H3 variant CENP-A/CENH3. Here, we provide evidence for the existence of two structurally distinct CENP-A populations that co-exist in human cells. CENP-A nucleosomes that are associated with the inner kinetochore appear stabilized in an octameric conformation, with restricted access to the nucleosomal DNA. In contrast, the bulk population of CENP-A nucleosomes have diminished heights and wrap DNA loosely. These data support a model where the inner kinetochore associates with a discrete fraction of stabilized octameric nucleosomes, but is surrounded by flexible bulk CENP-A pre-nucleosomes.

Scientific Focus Area: Chromosome Biology

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