High-resolution whole-genome sequencing reveals that specific chromatin domains from most human chromosomes associate with nucleoli.
High-resolution whole-genome sequencing reveals that specific chromatin domains from most human chromosomes associate with nucleoli.
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DOI：
10.1091/mbc.e10-06-0508
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发表时间：
2010-11-01
影响因子：
3.3
通讯作者：
Lamond AI
中科院分区：
文献类型：
--
作者：
van Koningsbruggen S;Gierlinski M;Schofield P;Martin D;Barton GJ;Ariyurek Y;den Dunnen JT;Lamond AI
我们使用比较基因组杂交、深度测序和光激活显微镜对核仁相关染色质进行全基因组高分辨率研究。我们展示了大多数染色体上与核仁相关的特定区域。这些区域富含at，富含抑制基因，并与核膜相关位点重叠。核空间主要由染色体区域和核体占据。尽管染色体的这种组织方式影响基因功能，但人们对核体在染色体区域组织中的作用知之甚少。核仁是研究得最好的亚核结构，形成于顶端染色体上的rRNA重复基因簇周围。除了rDNA外，其他染色质序列也环绕在核仁表面，甚至可能环入核仁。这些额外的核相关结构域（NADs）尚未被很好地表征。我们在这里提出了一个全基因组，高分辨率的分析染色质内源性核仁相关。我们使用了三种互补的方法，即荧光比较基因组杂交，高通量深度DNA测序和光激活结合延时荧光显微镜。数据表明，除了rDNA重复单位外，大多数人类染色体的特定序列以可复制和可遗传的方式与核仁相关联。NADs共同具有高密度的富含at的序列元件，低基因密度和统计上显著富集的转录抑制基因。出乎意料的是，直接DNA测序和荧光光激活数据都表明，某些染色质位点可以特异性地与核仁或核膜结合。
We present a genomewide, high-resolution study of nucleolar-associated chromatin using comparative genome hybridization, deep sequencing, and photoactivation microscopy. We show specific regions from most chromosomes associate with nucleoli. These regions are AT-rich, enriched in repressed genes, and overlap with nuclear lamina-associated loci. The nuclear space is mostly occupied by chromosome territories and nuclear bodies. Although this organization of chromosomes affects gene function, relatively little is known about the role of nuclear bodies in the organization of chromosomal regions. The nucleolus is the best-studied subnuclear structure and forms around the rRNA repeat gene clusters on the acrocentric chromosomes. In addition to rDNA, other chromatin sequences also surround the nucleolar surface and may even loop into the nucleolus. These additional nucleolar-associated domains (NADs) have not been well characterized. We present here a whole-genome, high-resolution analysis of chromatin endogenously associated with nucleoli. We have used a combination of three complementary approaches, namely fluorescence comparative genome hybridization, high-throughput deep DNA sequencing and photoactivation combined with time-lapse fluorescence microscopy. The data show that specific sequences from most human chromosomes, in addition to the rDNA repeat units, associate with nucleoli in a reproducible and heritable manner. NADs have in common a high density of AT-rich sequence elements, low gene density and a statistically significant enrichment in transcriptionally repressed genes. Unexpectedly, both the direct DNA sequencing and fluorescence photoactivation data show that certain chromatin loci can specifically associate with either the nucleolus, or the nuclear envelope.