Histone Modifications within the Human X Centromere Region
Histone Modifications within the Human X Centromere Region
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DOI：
10.1371/journal.pone.0006602
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发表时间：
2009-08-12
期刊：
影响因子：
3.7
通讯作者：
Sullivan, Beth A.
中科院分区：
文献类型：
--
作者：
Mravinac, Brankica;Sullivan, Lori L.;Sullivan, Beth A.
人类着丝粒是由高度有序的阿尔法卫星DNA阵列组成的多兆碱基区域，由无序的阿尔法卫星单体和其他重复元件与染色体臂分开。组装如此大的重复区域的复杂性限制了对着丝粒染色质组织的详细研究。然而，人类X着丝粒的基因组图谱为探索复杂基因座的基因组结构提供了新的机会。我们用芯片检测了修饰的组蛋白在多条X染色体着丝粒区域的分布。H3在赖氨酸4位发生甲基化，与CENP-A定位的高阶α卫星DXZ1重合。异染色组蛋白修饰分布在400-500kb的着丝粒周围区域。大量的α卫星和伽马卫星DNA被富含等染色质和异染色质修饰，这意味着一些着丝粒周围重复序列具有多重染色质特征。X着丝粒的部分截断导致CENP-A/CENP-A结构域的尺寸减小，并增加了侧翼着丝粒的异色修饰。虽然删除了类似于着丝粒DNA的1/3的缺失，但CENP-A与α卫星阵列大小的比例保持在相同的比例，这表明着丝粒DNA的有限但定义的线性区域对于着丝粒组装是必要的。我们的结果表明，人类X着丝粒含有多种类型的染色质，其结构类似于较小的真核着丝粒，并通过扩大或收缩结构域来响应结构变化。
Human centromeres are multi-megabase regions of highly ordered arrays of alpha satellite DNA that are separated from chromosome arms by unordered alpha satellite monomers and other repetitive elements. Complexities in assembling such large repetitive regions have limited detailed studies of centromeric chromatin organization. However, a genomic map of the human X centromere has provided new opportunities to explore genomic architecture of a complex locus. We used ChIP to examine the distribution of modified histones within centromere regions of multiple X chromosomes. Methylation of H3 at lysine 4 coincided with DXZ1 higher order alpha satellite, the site of CENP-A localization. Heterochromatic histone modifications were distributed across the 400-500 kb pericentromeric regions. The large arrays of alpha satellite and gamma satellite DNA were enriched for both euchromatic and heterochromatic modifications, implying that some pericentromeric repeats have multiple chromatin characteristics. Partial truncation of the X centromere resulted in reduction in the size of the CENP-A/Cenp-A domain and increased heterochromatic modifications in the flanking pericentromere. Although the deletion removed similar to 1/3 of centromeric DNA, the ratio of CENP-A to alpha satellite array size was maintained in the same proportion, suggesting that a limited, but defined linear region of the centromeric DNA is necessary for kinetochore assembly. Our results indicate that the human X centromere contains multiple types of chromatin, is organized similarly to smaller eukaryotic centromeres, and responds to structural changes by expanding or contracting domains.