Single-cell-resolved dynamics of chromatin architecture delineate cell and regulatory states in zebrafish embryos

Cell Genomics

Kenny Mattonet¹  Jan Philipp Junker²  David Garfield²  Marine Gil³  Scott Allen Lacadie³  Wolfgang Kopp⁴  Alison C. McGarvey⁵  Alexandra Trinks⁵  Daniela Panáková⁵  Rieke Kempfer⁵  Anne Margarete Merks⁵  Dubravka Vučićević⁵  Antje Hirsekorn⁶  Didier Y.R. Stainier⁷  Altuna Akalin⁷  Ilija Bilić⁸  Uwe Ohler⁸  Ana Pombo⁹ 

[1] Bioinformatics and Omics Data Science Platform, Berlin Institute for Medical Systems Biology, Max Delbrück Centre for Molecular Medicine, Berlin 10115, Germany;DZHK (German Centre for Cardiovascular Research), partner site Berlin, Berlin 13125, Germany;Institute for Biology, Humboldt Universität Berlin, Berlin 10115, Germany;Quantitative Developmental Biology, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin 10115, Germany;Computational Regulatory Genomics, Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine, Berlin 10115, Germany;Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim 61231, Germany;Electrochemical Signaling in Development and Disease, Max Delbrück Centre for Molecular Medicine, Berlin, Germany;Epigenetic Regulation and Chromatin Architecture, Berlin Institute for Medical Systems Biology, Max Delbrück Centre for Molecular Medicine, Berlin, Germany;IRI Life Sciences, Humboldt Universität Berlin, Berlin 10115, Germany;

关键词: zebrafish;    chromatin;    cis regulatory element;    enhancer;    promoter;    single-cell ATAC-seq;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: DNA accessibility of cis-regulatory elements (CREs) dictates transcriptional activity and drives cell differentiation during development. While many genes regulating embryonic development have been identified, the underlying CRE dynamics controlling their expression remain largely uncharacterized. To address this, we produced a multimodal resource and genomic regulatory map for the zebrafish community, which integrates single-cell combinatorial indexing assay for transposase-accessible chromatin with high-throughput sequencing (sci-ATAC-seq) with bulk histone PTMs and Hi-C data to achieve a genome-wide classification of the regulatory architecture determining transcriptional activity in the 24-h post-fertilization (hpf) embryo. We characterized the genome-wide chromatin architecture at bulk and single-cell resolution, applying sci-ATAC-seq on whole 24-hpf stage zebrafish embryos, generating accessibility profiles for ∼23,000 single nuclei. We developed a genome segmentation method, ScregSeg (single-cell regulatory landscape segmentation), for defining regulatory programs, and candidate CREs, specific to one or more cell types. We integrated the ScregSeg output with bulk measurements for histone post-translational modifications and 3D genome organization and identified new regulatory principles between chromatin modalities prevalent during zebrafish development. Sci-ATAC-seq profiling of npas4l/cloche mutant embryos identified novel cellular roles for this hematovascular transcriptional master regulator and suggests an intricate mechanism regulating its expression. Our work defines regulatory architecture and principles in the zebrafish embryo and establishes a resource of cell-type-specific genome-wide regulatory annotations and candidate CREs, providing a valuable open resource for genomics, developmental, molecular, and computational biology.

【 授权许可】

Unknown