التفاصيل البيبلوغرافية
| العنوان: |
Robust Hi-C Maps of Enhancer-Promoter Interactions Reveal the Function of Non-coding Genome in Neural Development and Diseases. |
| المؤلفون: |
Lu, Leina1 (AUTHOR), Liu, Xiaoxiao1 (AUTHOR), Huang, Wei-Kai1,2,3 (AUTHOR), Giusti-Rodríguez, Paola1,4 (AUTHOR), Cui, Jian1 (AUTHOR), Zhang, Shanshan1 (AUTHOR), Xu, Wanying1 (AUTHOR), Wen, Zhexing5 (AUTHOR), Ma, Shufeng6 (AUTHOR), Rosen, Jonathan D.7 (AUTHOR), Xu, Zheng4,7 (AUTHOR), Bartels, Cynthia F.1 (AUTHOR), Kawaguchi, Riki8 (AUTHOR), Hu, Ming9 (AUTHOR), Scacheri, Peter C.1 (AUTHOR), Rong, Zhili6,10 (AUTHOR), Li, Yun4,7 (AUTHOR), Sullivan, Patrick F.1,4,11,12 (AUTHOR), Song, Hongjun1,2,13,14,15 (AUTHOR), Ming, Guo-li1,2,3,13,14,16 (AUTHOR) gming@pennmedicine.upenn.edu |
| المصدر: |
Molecular Cell. Aug2020, Vol. 79 Issue 3, p521-521. 1p. |
| مصطلحات موضوعية: |
*NEURAL development, *ETIOLOGY of diseases, *CHROMATIN, *GENOMES, *DEVELOPMENTAL neurobiology |
| مستخلص: |
Genome-wide mapping of chromatin interactions at high resolution remains experimentally and computationally challenging. Here we used a low-input "easy Hi-C" protocol to map the 3D genome architecture in human neurogenesis and brain tissues and also demonstrated that a rigorous Hi-C bias-correction pipeline (HiCorr) can significantly improve the sensitivity and robustness of Hi-C loop identification at sub-TAD level, especially the enhancer-promoter (E-P) interactions. We used HiCorr to compare the high-resolution maps of chromatin interactions from 10 tissue or cell types with a focus on neurogenesis and brain tissues. We found that dynamic chromatin loops are better hallmarks for cellular differentiation than compartment switching. HiCorr allowed direct observation of cell-type- and differentiation-specific E-P aggregates spanning large neighborhoods, suggesting a mechanism that stabilizes enhancer contacts during development. Interestingly, we concluded that Hi-C loop outperforms eQTL in explaining neurological GWAS results, revealing a unique value of high-resolution 3D genome maps in elucidating the disease etiology. • HiCorr allows robust mapping of sub-TAD chromatin interactions with Hi-C • Low-input "easy Hi-C" protocol compatible with 50–100k cells • Enhancer loops and aggregates are better marks of cell identity than compartments • Chromatin loops outperform eQTLs in defining neurological GWAS target genes Lu et al. developed a rigorous Hi-C bias-correction pipeline to significantly improve the robustness of high-resolution chromatin interaction maps. With a new low-input "easy Hi-C" protocol, they mapped chromatin interactions in neural samples, defined cell-type-specific enhancer loops and aggregates, and concluded that Hi-C outperforms eQTL in explaining GWAS results. [ABSTRACT FROM AUTHOR] |
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