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 TopczewskiKai Wang, Glenn S. Gerhard, Ross C. Hardison, Ting Wang, Keith C. Cheng, Feng Yue*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)337-343
Number of pages7
Issue number7837
StatePublished - Dec 10 2020

ASJC Scopus subject areas

  • General


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