Conservation of chromatin organization within human and primate centromeres

Abstract

SummaryThe focal attachment of the kinetochore to the centromere core is essential for genome maintenance, yet the highly repetitive nature of human centromeres limits our understanding of their chromatin organization. We demonstrate that single-molecule chromatin fiber sequencing can uniquely resolve chromatin organization within centromeres at single-molecule and single-nucleotide resolution. We find that the centromere core contains a dichotomous chromatin organization not found elsewhere in the genome, which is characterized by highly accessible chromatin patches heterogeneously punctuated amongst tightly compacted nucleosome arrays. These highly accessible chromatin patches correspond to sites of kinetochore attachment, and clustered CENP-B occupancy within these patches phase nucleosome arrays to the alpha-satellite repeat. This dichotomous chromatin organization is conserved among humans despite the marked divergence of the underlying alpha-satellite organization and is similarly conserved in gibbon centromeres that lack alpha-satellite repeats, indicating that functional conservation within centromeres is mediated at the level of chromatin, not DNA sequence.HighlightsDichotomous accessible and compacted chromatin (dichromatin) marks centromere coresHighly accessible chromatin patches punctuate sites of kinetochore attachmentDichromatin can form irrespective of CENP-B occupancyConservation within centromeres is mediated at the level of chromatin, not DNA