Static and Dynamic DNA Loops form AP-1-Bound Activation Hubs during Macrophage Development
Static and Dynamic DNA Loops form AP-1-Bound Activation Hubs during Macrophage Development
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DOI：
10.1016/j.molcel.2017.08.006
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发表时间：
2017-09-21
期刊：
影响因子：
16
通讯作者：
Snyder, Michael P.
中科院分区：
文献类型：
--
作者：
Phanstiel, Douglas H.;Van Bortle, Kevin;Snyder, Michael P.
人类基因组的三维排列包括结构和调节染色质环的复杂网络，其对于协调人类发育期间的转录变化是重要的。为了更好地理解细胞分化过程中背景特异性3D染色质结构和转录的机制，我们在人单核细胞和分化的巨噬细胞中生成了DNA环的全面原位Hi-C图谱。我们表明，动态循环事件的监管，而不是结构的性质，并揭示了广泛的协调动态增强子活动在预先形成和收购的DNA环。增强子结合环的形成和预形成环的增强子活化一起在关键巨噬细胞基因处形成多环活化枢纽。激活枢纽连接每个启动子3.4个增强子，并表现出强烈的富集激活蛋白1（AP-1）结合事件，这表明涉及细胞类型特异性转录因子的多环激活枢纽代表了一类重要的调控染色质结构的时空控制转录。
The three-dimensional arrangement of the human genome comprises a complex network of structural and regulatory chromatin loops important for coordinating changes in transcription during human development. To better understand the mechanisms underlying context-specific 3D chromatin structure and transcription during cellular differentiation, we generated comprehensive in situ Hi-C maps of DNA loops in human monocytes and differentiated macrophages. We demonstrate that dynamic looping events are regulatory rather than structural in nature and uncover widespread coordination of dynamic enhancer activity at preformed and acquired DNA loops. Enhancer-bound loop formation and enhancer activation of preformed loops together form multi-loop activation hubs at key macrophage genes. Activation hubs connect 3.4 enhancers per promoter and exhibit a strong enrichment for activator protein 1 (AP-1)-binding events, suggesting that multi-loop activation hubs involving cell-type-specific transcription factors represent an important class of regulatory chromatin structures for the spatiotemporal control of transcription.