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A paucity of heterochromatin at functional human neocentromeres

DOI: 10.1186/1756-8935-3-6

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High-resolution chromatin immunoprecipitation (ChIP) on CHIP (microarray) analysis of three independent neocentromeres from chromosome 13q revealed that each neocentromere contained ~100 kb of centromere protein (CENP)-A in a two-domain organization. Additional CENP-A domains were observed in the vicinity of neocentromeres, coinciding with CpG islands at the 5' end of genes. Analysis of histone H3 dimethylated at lysine 4 (H3K4me2) revealed small domains at each neocentromere. However, these domains of H3K4me2 were also found in the equivalent non-neocentric chromosomes. A surprisingly minimal (~15 kb) heterochromatin domain was observed at one of the neocentromeres, which formed in an unusual transposon-free region distal to the CENP-A domains. Another neocentromere showed a distinct absence of nearby significant domains of heterochromatin. A subtle defect in centromere cohesion detected at these neocentromeres may be due to the paucity of heterochromatin domains.This high-resolution mapping suggests that H3K4me2 does not seem sufficiently abundant to play a structural role at neocentromeres, as proposed for endogenous centromeres. Large domains of heterochromatin also do not appear necessary for centromere function. Thus, this study provides important insight into the structural requirements of human centromere function.The centromere is the chromosomal locus responsible for the proper segregation of replicated sister chromatids to daughter cells during cell division. In all eukaryotes, the centromere is characterized by a unique chromatin structure that contains a centromere-specific histone 3 variant, called centromere protein (CENP)-A in mammals [1,2]. The kinetochore, a large multiprotein complex, is built onto this CENP-A chromatin and mediates microtubule attachment during mitosis and meiosis [3]. The CENP-A domain is flanked by heterochromatin, characterized by histone H3 methylated at lysine 9 (H3K9me), which may be important for centromeric chromatid cohe


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