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. SOURCE: Xiaoxiao Liu (xxl244@case.edu) - Fulai Jin Case Western Reserve University

Pluto Bioinformatics

GSE115407: Robust Hi-C maps of enhancer-promoter interactions reveal the function of non-coding genome in neural development and diseases