Integrated annotation and analysis of genomic features reveal new types of functional elements and large-scale epigenetic phenomena in the developing zebrafish

Abstract

Zebrafish, a popular model for embryonic development and for modelling human diseases, has so far lacked a systematic functional annotation programme akin to those in other animal models. To address this, we formed the international DANIO-CODE consortium and created the first central repository to store and process zebrafish developmental functional genomic data. Our Data Coordination Center (https://danio-code.zfin.org) combines a total of 1,802 sets of unpublished and reanalysed published genomics data, which we used to improve existing annotations and show its utility in experimental design. We identified over 140,000 cis-regulatory elements in development, including novel classes with distinct features dependent on their activity in time and space. We delineated the distinction between regulatory elements active during zygotic genome activation and those active during organogenesis, identifying new aspects of how they relate to each other. Finally, we matched regulatory elements and epigenomic landscapes between zebrafish and mouse and predict functional relationships between them beyond sequence similarity, extending the utility of zebrafish developmental genomics to mammals.

Zebrafish transposable elements show extensive diversification in age, genomic distribution, and developmental expression

“…Processed ATAC-seq BAM files mapped to GRCz11 genome for the Marlétaz et al (2018) study were downloaded from the DANIO-CODE ( Hörtenhuber et al 2020 ; Baranasic et al 2021 ) website (series DCD000433SR). BAM files were sorted by query name (-n) using SAMtools (version 1.10) ( Li et al 2009 ) and processed using Genrich ( , version 0.5_dev) with the following parameters: -t BAM -o OUT_Peak -f OUT_pq -k OUT_bdg -e chrM -j -y. bigWig tracks and heatmaps were produced using the deepTools suite (version 3.5.0) ( Ramírez et al 2016 ).…”

Integrative mapping of the dog epigenome: reference annotation for comparative inter-tissue and cross-species studies

“…The ENCODE [ 14,15,25,36 ], now in its phase 4, along with Roadmap Epigenomics consortia have pioneered yet the most comprehensive annotation of functional elements encoded in the human genome. Parallel to this, the mouse (C57BL/6J strain) ENCODE [ 16,36,44 ], modENCODE for worm (C. elegans) [ 79 ] and fly (D. melanogaster) [ 80 ], and DANIO-CODE for zebrafish (D. rerio) [ 81 ] consortia have been initiated, which by far provide the highest resolution epigenomes for such laboratory model organisms at scale. Such cataloging of epigenomes paved roadmaps toward better understanding the principles of genome architecture and function and gene regulation; and enabled the translation of biology between human and other organisms.…”

“…Per sample, we achieved an average of >111.2 million, >42.8 million, and >46.9 million mapped paired-end reads for RNAseq, ChIP-seq, and MBD-seq, respectively, substantially exceeding the ENCODE standards of >30 million reads, at least for both RNA-seq and ChIP-seq (Supplementary Data 1-3). Among the 11 tissues (cerebellum, cerebrum, colon, kidney, liver, lung, mammary gland, ovary, pancreas, spleen, and stomach), we obtained an average 40,034,81,814,119,198,35,043,71,362, and 300,036 peaks for H3K4me3, H3K4me1, H3K27ac, H3K27me3, H3K9me3, and MBD, with average size of 625, 431, 604, 358, 404, and 588 bp, and covering 1.1, 1.5, 3.1, 0.5, 1.2, and 7.6% of the entire dog genome, respectively. Following each NGS run, we implemented transcript integrity number (TIN) analysis to evaluate RNA integrity post-RNA-seq and strand crosscorrelation analysis to assess peak calling-independent quality check (QC) for both ChIP-seq and MBD-seq.…”

Epigenetic Regulation of Endothelial Cell Lineages During Zebrafish Development—New Insights From Technical Advances

“…This database has later been used to successfully identify a notch1b enhancer driving arterial expression in zebrafish ( Chiang et al, 2017 ), suggesting that despite its limitations, it can be used to retrieve vascular-specific enhancers. Data from the DANIO_CODE consortium ( Baranasic et al, 2021 , preprint) provides whole-body and a number of tissue-specific ChIP-seq datasets. The technique was successfully used on mouse and cultured endothelial cells in multiple studies ( Table 1 ), and recently it has been paired with transcriptomic and DNA methylation analysis to investigate the mechanisms underlying the segregation of lymphatic and blood endothelium in humans ( Tacconi et al, 2020 ).…”