Robust Hi-C maps of enhancer-promoter interactions reveal the function of non-coding genome in neural development and diseases

Despite recent progress in mammalian 3D genome studies, it remains experimentally and computationally challenging to identify chromatin interactions genome-wide. Here we developed a highly efficient “easy Hi-C” (eHi-C) protocol that generates high-yield libraries with 0.1 million cells. After rigorous bias-correction with a significantly improved Hi-C analysis pipeline, we can directly recognize the dynamic long- and short-range chromatin loops from contact heatmaps. We compared 10 ultra-deep Hi-C or eHi-C datasets (billion- read scale) from human tissue- or cell types focusing on brain and neurogenesis. We found that H3K9me3 marks a 3D genome compartmental barrier for induced pluripotency. Dynamic chromatin loops, but not genome compartments, are hallmarks of neuronal differentiation and neuron-related diseases. Interestingly, we observed many neuron-specific enhancer-promoter looping clusters spanning Mb-scale neighborhoods, supporting a phase-separation model leading to enhancer aggregation during brain development. Taken together, our 3D genome analyses shed light on the regulation of brain development and complex neuronal diseases. 3D genome structure mapping in human neurogenesis (from human induced pluripiotent stem cells to neural progenitor cells to neuron cells) using a newly designed easy Hi-C method ---------------------------------- GSM1267196: anchor_2_anchor.loop.H1.txt.gz GSM1267197: anchor_2_anchor.loop.H1.txt.gz GSM1055800: anchor_2_anchor.loop.IMR90.txt.gz GSM1055801: anchor_2_anchor.loop.IMR90.txt.gz GSM1154021: anchor_2_anchor.loop.IMR90.txt.gz GSM1154022: anchor_2_anchor.loop.IMR90.txt.gz GSM1154023: anchor_2_anchor.loop.IMR90.txt.gz GSM1154024: anchor_2_anchor.loop.IMR90.txt.gz GSM1055802: anchor_2_anchor.loop.IMR90.txt.gz GSM1055803: anchor_2_anchor.loop.IMR90.txt.gz GSM1154025: anchor_2_anchor.loop.IMR90.txt.gz GSM1154026: anchor_2_anchor.loop.IMR90.txt.gz GSM1154027: anchor_2_anchor.loop.IMR90.txt.gz GSM1154028: anchor_2_anchor.loop.IMR90.txt.gz GSM1181867: anchor_2_anchor.loop.GM12878.txt.gz GSM1181868: anchor_2_anchor.loop.GM12878.txt.gz GSM1551583: anchor_2_anchor.loop.GM12878.txt.gz GSM1551584: anchor_2_anchor.loop.GM12878.txt.gz GSM1551586: anchor_2_anchor.loop.GM12878.txt.gz GSM1608505: anchor_2_anchor.loop.GM12878.txt.gz GSM2054564: anchor_2_anchor.loop.CP.txt.gz GSM2054565: anchor_2_anchor.loop.CP.txt.gz GSM2054566: anchor_2_anchor.loop.CP.txt.gz GSM2054567: anchor_2_anchor.loop.GZ.txt.gz GSM2054568: anchor_2_anchor.loop.GZ.txt.gz GSM2054569: anchor_2_anchor.loop.GZ.txt.gz