The shared genomic architecture of human nucleolar organizer regions.
The shared genomic architecture of human nucleolar organizer regions.
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DOI：
10.1101/gr.157941.113
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发表时间：
2013-12
期刊：
影响因子：
7
通讯作者：
McStay B
中科院分区：
文献类型：
--
作者：
Floutsakou I;Agrawal S;Nguyen TT;Seoighe C;Ganley AR;McStay B
人类五条顶端着丝粒染色体的短臂含有指导核仁组装和功能的序列，核仁是核的关键功能域之一，但它们在目前的人类基因组组装中缺失。这里我们描述了这些人类核仁组织者的基因组结构。核糖体基因阵列的远端和近端的序列在端着丝粒染色体中是保守的，这表明它们是频繁重组的部位。尽管以前认为这两个侧翼区域是异染色质的，但对它们的表征表明，它们与基因组的其他常着色体区域具有相似的复杂基因组结构，但它们具有不同的基因组特征。近端序列几乎完全是分段复制的，类似于与着丝粒相邻的区域。相反，远端序列主要是顶端着丝粒短臂所特有的，并由一个非常大的反向重复序列主导。我们发现远端元件定位于核仁的外围，在那里它似乎锚定了核糖体基因重复。结合其复杂的染色质结构和转录活性，表明该区域参与了核仁组织。我们的结果为研究NORs在核仁形成和功能中的作用提供了一个平台，并为确定这些区域在众所周知的核仁与病理的经验关联中的作用打开了大门。
The short arms of the five acrocentric human chromosomes harbor sequences that direct the assembly and function of the nucleolus, one of the key functional domains of the nucleus, yet they are absent from the current human genome assembly. Here we describe the genomic architecture of these human nucleolar organizers. Sequences distal and proximal to ribosomal gene arrays are conserved among the acrocentric chromosomes, suggesting they are sites of frequent recombination. Although previously believed to be heterochromatic, characterization of these two flanking regions reveals that they share a complex genomic architecture similar to other euchromatic regions of the genome, but they have distinct genomic characteristics. Proximal sequences are almost entirely segmentally duplicated, similar to the regions bordering centromeres. In contrast, the distal sequence is predominantly unique to the acrocentric short arms and is dominated by a very large inverted repeat. We show that the distal element is localized to the periphery of the nucleolus, where it appears to anchor the ribosomal gene repeats. This, combined with its complex chromatin structure and transcriptional activity, suggests that this region is involved in nucleolar organization. Our results provide a platform for investigating the role of NORs in nucleolar formation and function, and open the door for determining the role of these regions in the well-known empirical association of nucleoli with pathology.
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影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
影响因子：
1.7
作者：
Jurka, J;Kapitonov, VV;Walichiewicz, J
通讯作者：
Walichiewicz, J
影响因子：
8
作者：
Hannan, KM;Hannan, RD;Rothblum, LI
通讯作者：
Rothblum, LI
影响因子：
9.2
作者：
Andersen, JS;Lyon, CE;Lamond, AI
通讯作者：
Lamond, AI
影响因子：
7
作者：
Lyle, Robert;Prandini, Paola;Antonarakis, Stylianos E.
通讯作者：
Antonarakis, Stylianos E.