A map of cis-regulatory elements and 3D genome structures in zebrafish

• Published in: Nature (London) Vol. 588; no. 7837; pp. 337 - 343
• Main Authors: Yang, Hongbo, Luan, Yu, Liu, Tingting, Lee, Hyung Joo, Fang, Li, Wang, Yanli, Wang, Xiaotao, Zhang, Bo, Jin, Qiushi, Ang, Khai Chung, Xing, Xiaoyun, Wang, Juan, Xu, Jie, Song, Fan, Sriranga, Iyyanki, Khunsriraksakul, Chachrit, Salameh, Tarik, Li, Daofeng, Choudhary, Mayank N. K., Topczewski, Jacek, Wang, Kai, Gerhard, Glenn S., Hardison, Ross C., Wang, Ting, Cheng, Keith C., Yue, Feng
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.12.2020; Nature Publishing Group
• Subjects: 38; 45; 45/15; 631/208/177; 631/208/514/2184; 631/337/100/101; Animals; Annotations; Bisulfite; Brain - metabolism; Breakpoints; Chromatin; Chromosome 4; Chromosomes; Conserved Sequence - genetics; Danio rerio; Deoxyribonucleic acid; DNA; DNA Methylation; DNA sequencing; Embryos; Enhancer Elements, Genetic - genetics; Epigenesis, Genetic; Evolution; Evolution, Molecular; Female; Gene Expression Profiling; Gene Regulatory Networks - genetics; Genes; Genetic aspects; Genetic research; Genome - genetics; Genomes; Genomics; Heterochromatin; Heterochromatin - chemistry; Heterochromatin - genetics; Heterochromatin - metabolism; Histone H3; Histones; Humanities and Social Sciences; Humans; Imaging, Three-Dimensional; Immunoprecipitation; Lysine; Male; Mice; Molecular Imaging; multidisciplinary; Neural coding; Organ Specificity; Physiological aspects; Promoter Regions, Genetic - genetics; Regulatory sequences; Regulatory Sequences, Nucleic Acid - genetics; Ribonucleic acid; RNA; Science; Science (multidisciplinary); Sex chromosomes; Single-Cell Analysis; Species Specificity; Transcription factors; Transposase; Zebra fish; Zebrafish; Zebrafish - genetics; United States
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-020-2962-9

The zebrafish ( Danio rerio ) has been widely used in the study of human disease and development, and about 70% of the protein-coding genes are conserved between the two species 1 . However, studies in zebrafish remain constrained by the sparse annotation of functional control elements in the zebrafish genome. Here we performed RNA sequencing, assay for transposase-accessible chromatin using sequencing (ATAC-seq), chromatin immunoprecipitation with sequencing, whole-genome bisulfite sequencing, and chromosome conformation capture (Hi-C) experiments in up to eleven adult and two embryonic tissues to generate a comprehensive map of transcriptomes, cis -regulatory elements, heterochromatin, methylomes and 3D genome organization in the zebrafish Tübingen reference strain. A comparison of zebrafish, human and mouse regulatory elements enabled the identification of both evolutionarily conserved and species-specific regulatory sequences and networks. We observed enrichment of evolutionary breakpoints at topologically associating domain boundaries, which were correlated with strong histone H3 lysine 4 trimethylation (H3K4me3) and CCCTC-binding factor (CTCF) signals. We performed single-cell ATAC-seq in zebrafish brain, which delineated 25 different clusters of cell types. By combining long-read DNA sequencing and Hi-C, we assembled the sex-determining chromosome 4 de novo. Overall, our work provides an additional epigenomic anchor for the functional annotation of vertebrate genomes and the study of evolutionarily conserved elements of 3D genome organization. A comprehensive map of transcriptomes, cis -regulatory elements, heterochromatin structure, the methylome and 3D genome organization in the zebrafish ( Danio rerio ) enables identification of species-specific and evolutionarily conserved regulatory features, and provides a foundation for modelling studies on human disease and development.