The long-range interaction landscape of gene promoters.
The long-range interaction landscape of gene promoters.
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DOI：
10.1038/nature11279
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发表时间：
2012-09-06
期刊：
影响因子：
64.8
通讯作者：
Dekker, Job
中科院分区：
文献类型：
--
作者：
Sanyal, Amartya;Lajoie, Bryan R.;Jain, Gaurav;Dekker, Job
人类基因组中巨大的非编码部分充斥着功能元件和致病调节变体。定义这些元件和远端靶基因之间关系的原则仍然未知。启动子和远端元件可以参与与基因调控有关的环状相互作用。在这里，我们应用染色体构象捕获碳拷贝，5C，全面询问转录起始位点（TSS）和远端元件之间的相互作用，在1%的人类基因组代表ENCODE试点项目区域。生成GM 12878、K562和HeLa-S3细胞的5C图谱，并将结果与来自ENCODE联盟的数据整合。在每个细胞系中，我们发现了启动子和远端位点之间的> 1，000种远程相互作用，其中包括类似于增强子，启动子和CTCF结合位点的元件。我们观察到基因表达，启动子-增强子相互作用和增强子RNA的存在之间的显着相关性。长程相互作用显示出显著的不对称性，与位于TSS上游~120 Kb的元素的相互作用存在偏差。长距离相互作用通常不被CTCF和粘着蛋白结合的位点阻断，这意味着这些位点中的许多不划分物理绝缘的基因结构域。此外，只有约7%的循环相互作用是与最近的基因，这表明基因组的接近不是一个简单的预测长距离相互作用。最后，启动子和远端元件参与多种长程相互作用，形成复杂的网络。我们的研究结果开始将基因和调控元件置于三维环境中，揭示它们的功能关系。
The vast non-coding portion of the human genome is awash in functional elements and disease-causing regulatory variants. The principles defining the relationships between these elements and distal target genes remain unknown. Promoters and distal elements can engage in looping interactions that have been implicated in gene regulation. Here we have applied chromosome conformation capture carbon copy, 5C, to comprehensively interrogate interactions between transcription start sites (TSSs) and distal elements in 1% of the human genome representing the ENCODE pilot project regions. 5C maps were generated for GM12878, K562 and HeLa-S3 cells and results were integrated with data from the ENCODE consortium. In each cell line we discovered >1,000 long-range interactions between promoters and distal sites that include elements resembling enhancers, promoters and CTCF-bound sites. We observed significant correlations between gene expression, promoter-enhancer interactions and the presence of enhancer RNAs. Long-range interactions display striking asymmetry with a bias for interactions with elements located ~120 Kb upstream of the TSS. Long-range interactions are often not blocked by sites bound by CTCF and cohesin implying that many of these sites do not demarcate physically insulated gene domains. Further, only ~7% of looping interactions are with the nearest gene, suggesting that genomic proximity is not a simple predictor for long-range interactions. Finally, promoters and distal elements are engaged in multiple long-range interactions to form complex networks. Our results start to place genes and regulatory elements in three-dimensional context, revealing their functional relationships.
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影响因子：
9.8
作者：
ENCODE Project Consortium
通讯作者：
ENCODE Project Consortium
α-珠蛋白基因结构域的三维折叠揭示了染色质球的形成。
影响因子：
16.8
作者：
通讯作者：
--
DOI：
10.1073/pnas.0605343103
发表时间：
2006-08-15
影响因子：
11.1
作者：
Gheldof, Nele;Tabuchi, Tornoko M.;Dekker, Job
通讯作者：
Dekker, Job
影响因子：
30.8
作者：
Zhao, Zhihu;Tavoosidana, Gholamreza;Ohlsson, Rolf
通讯作者：
Ohlsson, Rolf
影响因子：
7
作者：
Dostie, Josee;Richmond, Todd A.;Dekker, Job
通讯作者：
Dekker, Job