Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions
Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions
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DOI：
10.1038/nature06947
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发表时间：
2008-06-12
期刊：
影响因子：
64.8
通讯作者：
van Steensel, Bas
中科院分区：
文献类型：
--
作者：
Guelen, Lars;Pagie, Ludo;van Steensel, Bas
在间期细胞核中人类染色体的结构在很大程度上仍然未知。显微镜研究表明，染色体的特定区域紧邻核纤层（NL）（1 - 3）。这导致了一种观点，即某些基因组元件可能附着于核纤层，这可能有助于细胞核内染色体的空间组织。然而，人类基因组中在体内与核纤层相互作用的序列尚未被确定。在此，我们构建了人类成纤维细胞中整个基因组与核纤层成分相互作用位点的高分辨率图谱。该图谱显示，基因组 - 核纤层相互作用通过1300多个界限清晰的大片段区域发生，这些区域大小在0.1 - 10兆碱基之间。这些核纤层相关结构域（LADs）的典型特征是基因表达水平低，这表明LADs代表一种抑制性的染色质环境。LADs的边界由绝缘子蛋白CTCF、背向LADs的启动子或CpG岛划定，这提示了LADs限制的可能机制。综上所述，这些结果表明人类基因组被划分成大的、离散的区域，这些区域是细胞核内染色体组织的单元。
The architecture of human chromosomes in interphase nuclei is still largely unknown. Microscopy studies have indicated that specific regions of chromosomes are located in close proximity to the nuclear lamina (NL)(1-3). This has led to the idea that certain genomic elements may be attached to the NL, which may contribute to the spatial organization of chromosomes inside the nucleus. However, sequences in the human genome that interact with the NL in vivo have not been identified. Here we construct a high-resolution map of the interaction sites of the entire genome with NL components in human fibroblasts. This map shows that genome - lamina interactions occur through more than 1,300 sharply defined large domains 0.1 - 10 megabases in size. These lamina-associated domains ( LADs) are typified by low gene- expression levels, indicating that LADs represent a repressive chromatin environment. The borders of LADs are demarcated by the insulator protein CTCF, by promoters that are oriented away from LADs, or by CpG islands, suggesting possible mechanisms of LAD confinement. Taken together, these results demonstrate that the human genome is divided into large, discrete domains that are units of chromosome organization within the nucleus.