Abstract
Centromeres are defined by a specialized chromatin organization that includes nucleosomes that contain the centromeric histone variant centromere protein A (CENP-A) instead of canonical histone H3. Studies in various organisms have shown that centromeric chromatin (i.e., CENP-A chromatin or centrochromatin) exhibits plasticity, in that it can assemble on different types of DNA sequences. However, once established on a chromosome, the centromere is maintained at the same position. In humans, this location is the highly homogeneous repetitive DNA alpha satellite. Mislocalization of centromeric chromatin to atypical locations can lead to genome instability, indicating that restriction of centromeres to a distinct genomic position is important for cell and organism viability. Here, we describe a rearrangement of Homo sapiens chromosome 17 (HSA17) that has placed alpha satellite DNA next to euchromatin. We show that on this mutant chromosome, CENP-A chromatin has spread from the alpha satellite into the short arm of HSA17, establishing a ∼700 kb hybrid centromeric domain that spans both repetitive and unique sequences and changes the expression of at least one gene over which it spreads. Our results illustrate the plasticity of human centromeric chromatin and suggest that heterochromatin normally constrains CENP-A chromatin onto alpha satellite DNA. This work highlights that chromosome rearrangements, particularly those that remove the pericentromere, create opportunities for centromeric nucleosomes to move into non-traditional genomic locations, potentially changing the surrounding chromatin environment and altering gene expression.
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Acknowledgments
We thank Huntington Willard for the generous gift of the GM08148 cell line and L65-13A [del(17)] and L65-14A (normal HSA17) somatic cell hybrids. We are grateful to Dr. David Corcoran in the Duke Genomics and Bioinformatics Analysis Core Facility for assistance with genomic informatics. This research was partially supported by grants from the March of Dimes Foundation (06-FY10-294 and 1-FY13-517 to B.A.S.) and the National Institutes of Health (GM069514 and GM098500 to B.A.S.).
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Sullivan, L.L., Maloney, K.A., Towers, A.J. et al. Human centromere repositioning within euchromatin after partial chromosome deletion. Chromosome Res 24, 451–466 (2016). https://doi.org/10.1007/s10577-016-9536-6
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DOI: https://doi.org/10.1007/s10577-016-9536-6