Genomic size of CENP-A domain is proportional to total alpha satellite array size at human centromeres and expands in cancer cells.
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Human centromeres contain multi-megabase-sized arrays of alpha satellite DNA, a family of satellite DNA repeats based on a tandemly arranged 171 bp monomer. The centromere-specific histone protein CENP-A is assembled on alpha satellite DNA within the primary constriction, but does not extend along its entire length. CENP-A domains have been estimated to extend over 2,500 kb of alpha satellite DNA. However, these estimates do not take into account inter-individual variation in alpha satellite array sizes on homologous chromosomes and among different chromosomes. We defined the genomic distance of CENP-A chromatin on human chromosomes X and Y from different individuals. CENP-A chromatin occupied different genomic intervals on different chromosomes, but despite inter-chromosomal and inter-individual array size variation, the ratio of CENP-A to total alpha satellite DNA size remained consistent. Changes in the ratio of alpha satellite array size to CENP-A domain size were observed when CENP-A was overexpressed and when primary cells were transformed by disrupting interactions between the tumor suppressor protein Rb and chromatin. Our data support a model for centromeric domain organization in which the genomic limits of CENP-A chromatin varies on different human chromosomes, and imply that alpha satellite array size may be a more prominent predictor of CENP-A incorporation than chromosome size. In addition, our results also suggest that cancer transformation and amounts of centromeric heterochromatin have notable effects on the amount of alpha satellite that is associated with CENP-A chromatin.
Cell Line, Tumor
Cell Transformation, Neoplastic
Chromosomal Proteins, Non-Histone
Published Version (Please cite this version)10.1007/s10577-011-9208-5
Publication InfoBoivin, CD; Mravinac, B; Song, IY; Sullivan, Beth Ann; & Sullivan, LL (2011). Genomic size of CENP-A domain is proportional to total alpha satellite array size at human centromeres and expands in cancer cells. Chromosome Res, 19(4). pp. 457-470. 10.1007/s10577-011-9208-5. Retrieved from https://hdl.handle.net/10161/12806.
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Associate Professor of Molecular Genetics and Microbiology
Research in the Sullivan Lab is focused on chromosome organization, with a specific emphasis on the genomics and epigenetics of the chromosomal locus called the centromere and the formation and fate of chromosome abnormalities that are associated with birth defects, reproductive abnormalities, and cancer. The centromere is a specialized chromosomal site involved in chromosome architecture and movement, kinetochore function, heterochromatin assembly, and sister chromatid cohesion.Our