Capture-C reveals preformed chromatin interactions between HIF-binding sites and distant promoters.
Capture-C reveals preformed chromatin interactions between HIF-binding sites and distant promoters.
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DOI：
10.15252/embr.201642198
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发表时间：
2016-10
期刊：
影响因子：
7.7
通讯作者：
Mole DR
中科院分区：
文献类型：
--
作者：
Platt JL;Salama R;Smythies J;Choudhry H;Davies JO;Hughes JR;Ratcliffe PJ;Mole DR
缺氧诱导因子（HIF）指导广泛的转录级联反应，转导许多适应性反应缺氧。使用染色质免疫沉淀和转录谱分析的泛基因组分析揭示了大量通常与缺氧诱导转录物相关的HIF结合位点，即使在长染色体距离上也是如此。然而，这些研究没有定义HIF结合位点的特定靶点，也没有揭示HIF的诱导如何影响远距离连接的功能元件上的染色质构象。为了解决这些问题，我们部署了一种最近开发的染色体构象分析，可以从多个角度同时进行高分辨率分析。这些试验定义了基因间HIF结合区与缺氧诱导基因的一个或多个启动子之间的特异性长程相互作用，揭示了多个增强子-启动子、启动子-增强子和增强子-增强子相互作用的存在。然而，无论是缺氧对HIF的短期激活，还是von Hippel-Lindau（VHL）缺陷细胞中HIF的长期稳定，都不会极大地改变这些相互作用，这表明至少在这些条件下，HIF可以对预先存在的染色质-染色质相互作用模式起作用，这些模式定义了潜在的转录靶点，并允许缺氧应激快速激活基因。
Hypoxia‐inducible factor (HIF) directs an extensive transcriptional cascade that transduces numerous adaptive responses to hypoxia. Pan‐genomic analyses, using chromatin immunoprecipitation and transcript profiling, have revealed large numbers of HIF‐binding sites that are generally associated with hypoxia‐inducible transcripts, even over long chromosomal distances. However, these studies do not define the specific targets of HIF‐binding sites and do not reveal how induction of HIF affects chromatin conformation over distantly connected functional elements. To address these questions, we deployed a recently developed chromosome conformation assay that enables simultaneous high‐resolution analyses from multiple viewpoints. These assays defined specific long‐range interactions between intergenic HIF‐binding regions and one or more promoters of hypoxia‐inducible genes, revealing the existence of multiple enhancer–promoter, promoter–enhancer, and enhancer–enhancer interactions. However, neither short‐term activation of HIF by hypoxia, nor long‐term stabilization of HIF in von Hippel–Lindau (VHL)‐defective cells greatly alters these interactions, indicating that at least under these conditions, HIF can operate on preexisting patterns of chromatin–chromatin interactions that define potential transcriptional targets and permit rapid gene activation by hypoxic stress.
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影响因子：
64.8
作者：
Jin, Fulai;Li, Yan;Dixon, Jesse R.;Selvaraj, Siddarth;Ye, Zhen;Lee, Ah Young;Yen, Chia-An;Schmitt, Anthony D.;Espinoza, Celso A.;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
--
作者：
Leisz S;Schulz K;Erb S;Oefner P;Dettmer K;Mougiakakos D;Wang E;Marincola FM;Stehle F;Seliger B
通讯作者：
Seliger B
影响因子：
41.5
作者：
Koury, Mark J.;Haase, Volker H.
通讯作者：
Haase, Volker H.
影响因子：
7.7
作者：
Choudhry, Hani;Schoedel, Johannes;Oikonomopoulos, Spyros;Camps, Carme;Grampp, Steffen;Harris, Adrian L.;Ratcliffe, Peter J.;Ragoussis, Jiannis;Mole, David R.
通讯作者：
Mole, David R.
影响因子：
9.9
作者：
Eijkelenboom, Astrid;Mokry, Michal;Burgering, Boudewijn M. T.
通讯作者：
Burgering, Boudewijn M. T.