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. Overall design: 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