Human centromere repositioning within euchromatin after partial chromosome deletion.
Human centromere repositioning within euchromatin after partial chromosome deletion.
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DOI：
10.1007/s10577-016-9536-6
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发表时间：
2016-12
期刊：
影响因子：
--
通讯作者：
Sullivan BA
中科院分区：
文献类型：
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作者：
Sullivan LL;Maloney KA;Towers AJ;Gregory SG;Sullivan BA
着丝粒由特殊的染色质组织定义，其中包括含有着丝粒组蛋白变体 CENP-A 而不是典型组蛋白 H3 的核小体。对各种生物体的研究表明，着丝粒染色质（即 CENP-A 染色质或中心染色质）具有可塑性，因为它可以组装在不同类型的 DNA 序列上。然而，一旦在染色体上建立，着丝粒就会保持在相同的位置。在人类中，这个位置是高度同质的重复 DNA α 卫星。着丝粒染色质错误定位到非典型位置可能导致基因组不稳定，这表明着丝粒限制在不同的基因组位置对于细胞和生物体的生存能力很重要。在这里，我们描述了智人 17 号染色体 (HSA17) 的重排，将 α 卫星 DNA 置于常染色质旁边。我们发现，在这个突变染色体上，CENP-A 染色质已从 α 卫星扩散到 HSA17 的短臂中，建立了一个约 700kb 的混合着丝粒结构域，该结构域跨越重复序列和独特序列，并改变了其所扩散的至少一个基因的表达。我们的结果说明了人类着丝粒染色质的可塑性，并表明异染色质通常将 CENP-A 染色质限制在 α 卫星 DNA 上。这项工作强调，染色体重排，特别是那些去除着丝粒周围的重排，为着丝粒核小体进入非传统基因组位置创造了机会，可能改变周围的染色质环境并改变基因表达。
Centromeres are defined by a specialized chromatin organization that includes nucleosomes that contain the centromeric histone variant 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 ~700kb 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.