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Functional epialleles at an endogenous human centromere.

dc.contributor.author Ferris, A
dc.contributor.author Maloney, KA
dc.contributor.author Matheny, JE
dc.contributor.author Merrett, SL
dc.contributor.author Strome, ED
dc.contributor.author Sullivan, Beth Ann
dc.contributor.author Sullivan, LL
dc.coverage.spatial United States
dc.date.accessioned 2016-09-28T22:16:21Z
dc.date.issued 2012-08-21
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/22847449
dc.identifier 1203126109
dc.identifier.uri http://hdl.handle.net/10161/12802
dc.description.abstract Human centromeres are defined by megabases of homogenous alpha-satellite DNA arrays that are packaged into specialized chromatin marked by the centromeric histone variant, centromeric protein A (CENP-A). Although most human chromosomes have a single higher-order repeat (HOR) array of alpha satellites, several chromosomes have more than one HOR array. Homo sapiens chromosome 17 (HSA17) has two juxtaposed HOR arrays, D17Z1 and D17Z1-B. Only D17Z1 has been linked to CENP-A chromatin assembly. Here, we use human artificial chromosome assembly assays to show that both D17Z1 and D17Z1-B can support de novo centromere assembly independently. We extend these in vitro studies and demonstrate, using immunostaining and chromatin analyses, that in human cells the centromere can be assembled at D17Z1 or D17Z1-B. Intriguingly, some humans are functional heterozygotes, meaning that CENP-A is located at a different HOR array on the two HSA17 homologs. The site of CENP-A assembly on HSA17 is stable and is transmitted through meiosis, as evidenced by inheritance of CENP-A location through multigenerational families. Differences in histone modifications are not linked clearly with active and inactive D17Z1 and D17Z1-B arrays; however, we detect a correlation between the presence of variant repeat units of D17Z1 and CENP-A assembly at the opposite array, D17Z1-B. Our studies reveal the presence of centromeric epialleles on an endogenous human chromosome and suggest genomic complexities underlying the mechanisms that determine centromere identity in humans.
dc.language eng
dc.relation.ispartof Proc Natl Acad Sci U S A
dc.relation.isversionof 10.1073/pnas.1203126109
dc.subject Alleles
dc.subject Animals
dc.subject Autoantigens
dc.subject Centromere
dc.subject Centromere Protein B
dc.subject Chromatin
dc.subject Chromatin Assembly and Disassembly
dc.subject Chromosomal Proteins, Non-Histone
dc.subject Chromosomes
dc.subject Heterochromatin
dc.subject Heterozygote
dc.subject Humans
dc.subject Kinetochores
dc.subject Meiosis
dc.subject Mice
dc.subject Polymorphism, Genetic
dc.title Functional epialleles at an endogenous human centromere.
dc.type Journal article
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/22847449
pubs.begin-page 13704
pubs.end-page 13709
pubs.issue 34
pubs.organisational-group Basic Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Molecular Genetics and Microbiology
pubs.organisational-group School of Medicine
pubs.publication-status Published
pubs.volume 109
dc.identifier.eissn 1091-6490


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