A unique chromatin complex occupies young α-satellite arrays of human centromeres.

Sci Adv

Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA ; Howard Hughes Medical Institute, Seattle, WA 98109, USA.

Published: February 2015

The intractability of homogeneous α-satellite arrays has impeded understanding of human centromeres. Artificial centromeres are produced from higher-order repeats (HORs) present at centromere edges, although the exact sequences and chromatin conformations of centromere cores remain unknown. We use high-resolution chromatin immunoprecipitation (ChIP) of centromere components followed by clustering of sequence data as an unbiased approach to identify functional centromere sequences. We find that specific dimeric α-satellite units shared by multiple individuals dominate functional human centromeres. We identify two recently homogenized α-satellite dimers that are occupied by precisely positioned CENP-A (cenH3) nucleosomes with two ~100-base pair (bp) DNA wraps in tandem separated by a CENP-B/CENP-C-containing linker, whereas pericentromeric HORs show diffuse positioning. Precise positioning is largely maintained, whereas abundance decreases exponentially with divergence, which suggests that young α-satellite dimers with paired ~100-bp particles mediate evolution of functional human centromeres. Our unbiased strategy for identifying functional centromeric sequences should be generally applicable to tandem repeat arrays that dominate the centromeres of most eukaryotes.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410388PMC
http://dx.doi.org/10.1126/sciadv.1400234DOI Listing

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