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The development and application of 3D genome mapping technology

日期: 2019-04-02
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题目: The development and application of 3D genome mapping technology
讲座人:Meizhen Zheng, Ph.D.
Associate Research Scientist,
The Jackson Laboratory for Genomic Medicine
时间:2019年5月7日(星期二)15:00-16:00
地点:吕志和楼B106
摘要:
The genomes of multicellular organisms are extensively folded into 3D chromosome territories within the nucleus. It has been proposed that genome organization and function involve the interplay of proteins, RNAs, and chromatin architectures. So it is very important for developing 3D genome mapping methods to identify the structures and dynamic organization of the genome. Here we describe a strategy for multiplex chromatin-interaction analysis via droplet-based and barcode-linked sequencing, named ChIA-Drop. We demonstrate the robustness of ChIA-Drop in capturing complex chromatin interactions with single-molecule precision, which has not been possible using methods based on population-level pairwise contacts, such as Hi-C and ChIA-PET. In addition, we report multivalent interplays in Drosophila cells involving RNA Polymerase II (RNAPII), nuclear RNAs, and chromatin interactions. Using a novel genomic approach (pRChIA-PET) for protein-RNA-chromatin interactions, we discovered that an extensive combination of nuclear RNAs cooperatively act in trans and co-localize with RNAPII and associated protein cofactors at chromatin interaction loci of active promoters and enhancers. We are planning to apply the 3D genome methods to elucidate how proteins, RNAs, and chromatin DNAs, organize into 3D chromatin structure, and how to affect or regulate disease-related genes expression, and then classify the topological structure type with epigenetic modification and chromatin state, offering 3D genome structure references, furthermore identifying disease-related therapeutic targets.
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