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

Hongbo Yang, Yu Luan, Tingting Liu, Hyung Joo Lee, Li Fang, Yanli Wang, Xiaotao Wang, Bo Zhang, Qiushi Jin, Khai Chung Ang, Xiaoyun Xing, Juan Wang, Jie Xu, Fan Song, Iyyanki Sriranga, Chachrit Khunsriraksakul, Tarik Salameh, Daofeng Li, Mayank N. K. Choudhary, Jacek Topczewski, Kai Wang, Glenn S. Gerhard, Ross C. Hardison, Ting Wang, Keith C. Cheng and Feng Yue ()
Additional contact information
Hongbo Yang: Feinberg School of Medicine Northwestern University
Yu Luan: Feinberg School of Medicine Northwestern University
Tingting Liu: Feinberg School of Medicine Northwestern University
Hyung Joo Lee: Washington University School of Medicine
Li Fang: Children’s Hospital of Philadelphia
Yanli Wang: The Pennsylvania State University
Xiaotao Wang: Feinberg School of Medicine Northwestern University
Bo Zhang: The Pennsylvania State University
Qiushi Jin: Feinberg School of Medicine Northwestern University
Khai Chung Ang: The Pennsylvania State University
Xiaoyun Xing: Washington University School of Medicine
Juan Wang: Feinberg School of Medicine Northwestern University
Jie Xu: Feinberg School of Medicine Northwestern University
Fan Song: The Pennsylvania State University
Iyyanki Sriranga: Feinberg School of Medicine Northwestern University
Chachrit Khunsriraksakul: The Pennsylvania State University
Tarik Salameh: The Pennsylvania State University
Daofeng Li: Washington University School of Medicine
Mayank N. K. Choudhary: Washington University School of Medicine
Jacek Topczewski: Northwestern University Feinberg School of Medicine
Kai Wang: Children’s Hospital of Philadelphia
Glenn S. Gerhard: Lewis Katz School of Medicine at Temple University
Ross C. Hardison: Pennsylvania State University
Ting Wang: Washington University School of Medicine
Keith C. Cheng: The Pennsylvania State University
Feng Yue: Feinberg School of Medicine Northwestern University

Nature, 2020, vol. 588, issue 7837, 337-343

Abstract: Abstract 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 species1. 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.

Date: 2020
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DOI: 10.1038/s41586-020-2962-9

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