title: Human centromere repositioning within euchromatin after partial chromosome deletion.
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.
authors: Department of Molecular Genetics and Microbiology, Duke University School of Medicine, DUMC 3054, Durham, NC, 27710, USA.
authors: Lori L
authors: LL
authors: Sullivan
authors: Department of Molecular Genetics and Microbiology, Duke University School of Medicine, DUMC 3054, Durham, NC, 27710, USA.|Department of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
authors: Kristin A
authors: KA
authors: Maloney
authors: University Program in Genetics and Genomics, Duke University School of Medicine, Durham, NC, 27710, USA.|Quintiles, 4820 Emperor Blvd., Durham, NC, 27703, USA.
authors: Aaron J
authors: AJ
authors: Towers
authors: Department of Medicine, Duke Molecular Physiology Institute, 300 N. Duke Street, Durham, NC, 27701, USA.|Division of Human Genetics, Duke University School of Medicine, Durham, NC, 27710, USA.
authors: Simon G
authors: SG
authors: Gregory
authors: Department of Molecular Genetics and Microbiology, Duke University School of Medicine, DUMC 3054, Durham, NC, 27710, USA. beth.sullivan@duke.edu.|Quintiles, 4820 Emperor Blvd., Durham, NC, 27703, USA. beth.sullivan@duke.edu.
authors: Beth A
authors: BA
authors: Sullivan
mesh_terms: D001324:Autoantigens / Q000378:metabolism; D002503:Centromere / Q000378:metabolism*; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002877:Chromosomes, Human; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D004276:DNA, Satellite / Q000378:metabolism; D022041:Euchromatin / Q000378:metabolism*; D006801:Humans; D009707:Nucleosomes / Q000378:metabolism; D058496:Smith-Magenis Syndrome / Q000235:genetics
chemical_list: D001324:Autoantigens; C000619700:CENPA protein, human; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; D004276:DNA, Satellite; D022041:Euchromatin; D009707:Nucleosomes
keywords: Alpha satellite; CENP-A; Histone; Neocentromere; Transcription; Transposable element