Project description:3D structure of chromatin is thought to be critical for the regulation of gene expression during development. Here we employ the Micro-C assay to achieve 100 bp resolution for the genome organization of Drosophila melanogaster throughout the first half of embryogenesis. The resulting contact maps enable the identification of fine-scaled structures such as individual loops and boundaries delineating TADs. We observe that 3D structures form prior to zygotic genome activation in precellular embryos, and many of these organizational features persist during successive mitotic cycles. 3D structures are classified through the use of 149 ChIP-seq datasets. We present evidence for specialized elements associated with housekeeping genes that are enriched for BEAF-32 but not CTCF. We also characterize a distinct class of elements associated with developmental gene regulation that are enriched with GAF and Zld binding. This binding is maintained during mitotic cycles and exhibits evolutionary conservation of both sequence and 3D structures. In sum, this work provides a comprehensive genome-wide characterization at unprecedented resolution of the role of 3D chromatin organization in gene regulation during development. We propose that the 3D organization of the pre-cellular embryo facilitates deployment of the developmental control genes defining the Drosophila fate map.
Project description:The zebrafish has been widely used for the study of human disease and development, as ~70% of the protein-coding genes are conserved between the two species. Annotation of functional control elements of the zebrafish genome, however, has lagged behind that of other model systems such as mouse and Drosophila. Based on multi-omics approaches taken in the ENCODE and Roadmap Epigenomics projects, we performed RNA-seq, ATAC-seq, ChIP-seq and Hi-C experiments in ten adult and two embryonic tissues to generate a comprehensive map of transcriptomes and regulatory elements in the zebrafish Tuebingen reference strain. Overall, we have identified 235,596 cis-regulatory elements, which potentially shape the tissue-specific and developmental-stage-specific gene expression in zebrafish. A comparison of zebrafish, human, and mouse regulatory elements allowed us to identify both evolutionarily conserved and species-specific regulatory sequences. Furthermore, through the analysis of Hi-C data in zebrafish brain and muscle, we observed different levels of 3D genome organization, including compartment, topological associating domains (TADs), and chromatin loops in zebrafish. A subset of TADs are deeply conserved between zebrafish and human. This work provides an additional epigenomic anchor for the functional annotation of vertebrate genomes and the study of evolutionally conserved elements of 3D genome organization.
Project description:This project is based on visualizing the chemical and microbiological composition of individuals of Colostethus panamensis (Dendrobatidae), through the creation of a topographic map of the surface of their skin in 3D
Project description:RNA molecules not only carry genetic information like DNA, but also folds into exquisite 3D structures like proteins. Despite strong interests in RNA biology and their medical applications, RNA structure determination in vivo remained a long-standing problem. Here we developed a new technology to directly determine RNA structures in vivo, termed SHARC-seq. Applying SHARC-seq, spatial distances among nucleotides can be measured and used to rebuild in vivo RNA 3D structure and dynamics.
Project description:This project is based on visualizing the chemical and microbiological composition of individuals of Colostethus panamensis (Dendrobatidae), through the creation of a topographic map of the surface of their skin in 3D
Project description:In the metazoan genome, regulatory DNA elements called enhancers govern the precise spatiotemporal patterns of gene expression in specific cell types. However, how enhancers are spatially organized to regulate target genes remains poorly understood. Here, by improving the spatial resolution of single-cell 3D genome mapping to 5 kb with micrococcal nuclease in our new single-cell Micro-C method, we report a specialized 3D structure of enhancers termed “promoter stripes,” which start at the transcription start site (TSS) and extend in the direction of transcription on the contact map, linking the promoter to multiple downstream enhancers. Promoter stripes are formed by cohesin-mediated loop extrusion, which potentially brings multiple enhancers to the promoter. Furthermore, with high-resolution single-cell chromatin structures, we observed the prevalence of multi-enhancer hubs on genes with promoter stripes, wherein multiple enhancers form spatial cluster associating its promoter. Such observation was only made possible by single-cell 3D genome with the improved resolution.
Project description:In the metazoan genome, regulatory DNA elements called enhancers govern the precise spatiotemporal patterns of gene expression in specific cell types. However, how enhancers are spatially organized to regulate target genes remains poorly understood. Here, by improving the spatial resolution of single-cell 3D genome mapping to 5 kb with micrococcal nuclease in our new single-cell Micro-C method, we report a specialized 3D structure of enhancers termed “promoter stripes,” which start at the transcription start site (TSS) and extend in the direction of transcription on the contact map, linking the promoter to multiple downstream enhancers. Promoter stripes are formed by cohesin-mediated loop extrusion, which potentially brings multiple enhancers to the promoter. Furthermore, with high-resolution single-cell chromatin structures, we observed the prevalence of multi-enhancer hubs on genes with promoter stripes, wherein multiple enhancers form spatial cluster associating its promoter. Such observation was only made possible by single-cell 3D genome with the improved resolution.
Project description:In the metazoan genome, regulatory DNA elements called enhancers govern the precise spatiotemporal patterns of gene expression in specific cell types. However, how enhancers are spatially organized to regulate target genes remains poorly understood. Here, by improving the spatial resolution of single-cell 3D genome mapping to 5 kb with micrococcal nuclease in our new single-cell Micro-C method, we report a specialized 3D structure of enhancers termed “promoter stripes,” which start at the transcription start site (TSS) and extend in the direction of transcription on the contact map, linking the promoter to multiple downstream enhancers. Promoter stripes are formed by cohesin-mediated loop extrusion, which potentially brings multiple enhancers to the promoter. Furthermore, with high-resolution single-cell chromatin structures, we observed the prevalence of multi-enhancer hubs on genes with promoter stripes, wherein multiple enhancers form spatial cluster associating its promoter. Such observation was only made possible by single-cell 3D genome with the improved resolution.
Project description:In the metazoan genome, regulatory DNA elements called enhancers govern the precise spatiotemporal patterns of gene expression in specific cell types. However, how enhancers are spatially organized to regulate target genes remains poorly understood. Here, by improving the spatial resolution of single-cell 3D genome mapping to 5 kb with micrococcal nuclease in our new single-cell Micro-C method, we report a specialized 3D structure of enhancers termed “promoter stripes,” which start at the transcription start site (TSS) and extend in the direction of transcription on the contact map, linking the promoter to multiple downstream enhancers. Promoter stripes are formed by cohesin-mediated loop extrusion, which potentially brings multiple enhancers to the promoter. Furthermore, with high-resolution single-cell chromatin structures, we observed the prevalence of multi-enhancer hubs on genes with promoter stripes, wherein multiple enhancers form spatial cluster associating its promoter. Such observation was only made possible by single-cell 3D genome with the improved resolution.