报告人：Dr. Meizhen Zheng
摘要：The genomes of multicellular organisms are extensively folded into 3D chromosome territories within the nucleus. Advanced 3D genome-mapping methods that combine proximity ligation and high-throughput sequencing (such as chromosome conformation capture, Hi-C), and chromatin immunoprecipitation techniques (such as chromatin interaction analysis by paired-end tag sequencing, ChIA-PET), have revealed topologically associating domains (TADs) with frequent chromatin contacts, and have identified chromatin loops mediated by specific protein factors for insulation and regulation of transcription. However, these methods rely on pairwise proximity ligation and reflect population-level views, and thus cannot reveal the detailed nature of chromatin interactions. Although single-cell Hi-C potentially overcomes this issue, this method may be limited by the sparsity of data that is inherent to current single-cell assays. Recent advances in microfluidics have opened opportunities for droplet-based genomic analysis but this approach has not yet been adapted for chromatin interaction analysis. Here we describe a strategy for multiplex chromatin-interaction analysis via droplet-based and barcode-linked sequencing, which we name 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. By applying ChIA-Drop to Drosophila cells, we show that chromatin topological structures predominantly consist of multiplex chromatin interactions with high heterogeneity; ChIA-Drop also reveals promoter-centered multivalent interactions, which provide topological insights into transcription.
报告人简介：Dr. Meizhen Zheng got her Ph.D from Sun Yat-Sen University Cancer Center. Currently, she is working at The Jackson Laboratory for Genomic Medicine (Connecticut, U.S.) as Associate Research Scientist. Her primary research is focusing on novel technology development for understanding 3D genome structures and functions. And she just developed a novel method for Multiplex Chromatin Interaction Analysis with Single-Molecule Precision (ChIA-Drop). ChIA-Drop is a strategy for analyzing multiplex chromatin interactions novel method using droplet-based and barcode-linked sequencing captures multiplex chromatin interactions at with single-molecule precision, and provides topological insight into chromatin structures and gene transcription.