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Decreased Enhancer-Promoter Proximity Accompanying Enhancer Activation.
Molecular Cell ( IF 14.5 ) Pub Date : 2019-09-04 , DOI: 10.1016/j.molcel.2019.07.038 Nezha S Benabdallah 1 , Iain Williamson 2 , Robert S Illingworth 2 , Lauren Kane 2 , Shelagh Boyle 2 , Dipta Sengupta 2 , Graeme R Grimes 2 , Pierre Therizols 3 , Wendy A Bickmore 2
Molecular Cell ( IF 14.5 ) Pub Date : 2019-09-04 , DOI: 10.1016/j.molcel.2019.07.038 Nezha S Benabdallah 1 , Iain Williamson 2 , Robert S Illingworth 2 , Lauren Kane 2 , Shelagh Boyle 2 , Dipta Sengupta 2 , Graeme R Grimes 2 , Pierre Therizols 3 , Wendy A Bickmore 2
Affiliation
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Enhancers can regulate the promoters of their target genes over very large genomic distances. It is widely assumed that mechanisms of enhancer action involve the reorganization of three-dimensional chromatin architecture, but this is poorly understood. The predominant model involves physical enhancer-promoter interaction by looping out the intervening chromatin. However, studying the enhancer-driven activation of the Sonic hedgehog gene (Shh), we have identified a change in chromosome conformation that is incompatible with this simple looping model. Using super-resolution 3D-FISH and chromosome conformation capture, we observe a decreased spatial proximity between Shh and its enhancers during the differentiation of embryonic stem cells to neural progenitors. We show that this can be recapitulated by synthetic enhancer activation, is impeded by chromatin-bound proteins located between the enhancer and the promoter, and appears to involve the catalytic activity of poly (ADP-ribose) polymerase. Our data suggest that models of enhancer-promoter communication need to encompass chromatin conformations other than looping.
中文翻译：
伴随增强子激活降低的增强子-启动子邻近度。
增强子可以在很大的基因组距离上调节其靶基因的启动子。人们普遍认为，增强子作用的机制涉及三维染色质结构的重组，但是对此知之甚少。主要模型涉及通过介入中间的染色质来促进物理增强子与启动子的相互作用。但是，通过研究Sonic刺猬基因（Shh）的增强子驱动的激活，我们发现了染色体构象的变化，该变化与这种简单的环状模型不兼容。使用超高分辨率的3D FISH和染色体构象捕获，我们观察到胚胎干细胞向神经祖细胞分化过程中Shh及其增强子之间的空间邻近性降低。我们证明了合成增强子的激活可以概括这一点，位于增强子和启动子之间的与染色质结合的蛋白阻碍了这种蛋白的表达，并且似乎涉及聚（ADP-核糖）聚合酶的催化活性。我们的数据表明，增强子-启动子通信的模型需要包含除环以外的染色质构象。
更新日期：2019-09-05
中文翻译：
伴随增强子激活降低的增强子-启动子邻近度。
增强子可以在很大的基因组距离上调节其靶基因的启动子。人们普遍认为，增强子作用的机制涉及三维染色质结构的重组，但是对此知之甚少。主要模型涉及通过介入中间的染色质来促进物理增强子与启动子的相互作用。但是，通过研究Sonic刺猬基因（Shh）的增强子驱动的激活，我们发现了染色体构象的变化，该变化与这种简单的环状模型不兼容。使用超高分辨率的3D FISH和染色体构象捕获，我们观察到胚胎干细胞向神经祖细胞分化过程中Shh及其增强子之间的空间邻近性降低。我们证明了合成增强子的激活可以概括这一点，位于增强子和启动子之间的与染色质结合的蛋白阻碍了这种蛋白的表达，并且似乎涉及聚（ADP-核糖）聚合酶的催化活性。我们的数据表明，增强子-启动子通信的模型需要包含除环以外的染色质构象。
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