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多组学图谱结合功能分层和斑马鱼顺式调控元件的发育动力学

Multiomic atlas with functional stratification and developmental dynamics of zebrafish cis-regulatory elements.

机构信息

MRC London Institute of Medical Sciences, London, UK.

Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK.

出版信息

Nat Genet. 2022 Jul;54(7):1037-1050. doi: 10.1038/s41588-022-01089-w. Epub 2022 Jul 4.


DOI:10.1038/s41588-022-01089-w
PMID:35789323
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9279159/
Abstract

Zebrafish, a popular organism for studying embryonic development and for modeling human diseases, has so far lacked a systematic functional annotation program akin to those in other animal models. To address this, we formed the international DANIO-CODE consortium and created a 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 Our data coordination center ( https://danio-code.zfin.org ) combines a total of 1,802 sets of unpublished and re-analyzed published genomic data, which we used to improve existing annotations and show its utility in experimental design. We identified over 140,000 cis-regulatory elements throughout development, including classes with distinct features dependent on their activity in time and space. We delineated the distinct distance topology and chromatin features between regulatory elements active during zygotic genome activation and those active during organogenesis. Finally, we matched regulatory elements and epigenomic landscapes between zebrafish and mouse and predicted functional relationships between them beyond sequence similarity, thus extending the utility of zebrafish developmental genomics to mammals.

摘要

斑马鱼是一种常用于研究胚胎发育和人类疾病模型的生物,但它一直缺乏类似于其他动物模型的系统功能注释计划。为了解决这个问题,我们成立了国际 DANIO-CODE 联盟,并创建了一个中央存储库来存储和处理斑马鱼发育功能基因组数据。我们的数据协调中心(https://danio-code.zfin.org)结合了总共 1802 组未发表和重新分析的已发表基因组数据,我们利用这些数据来改进现有的注释,并展示其在实验设计中的实用性。我们在整个发育过程中鉴定了超过 140000 个顺式调控元件,包括根据其在时间和空间上的活性具有不同特征的类别。我们描绘了在合子基因组激活期间和在器官发生期间活跃的调控元件之间独特的距离拓扑和染色质特征。最后,我们在斑马鱼和小鼠之间匹配了调控元件和表观基因组景观,并预测了它们之间除了序列相似性之外的功能关系,从而将斑马鱼发育基因组学的应用扩展到了哺乳动物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a43a/9279159/f61734823827/41588_2022_1089_Fig18_ESM.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a43a/9279159/a076f31575e1/41588_2022_1089_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a43a/9279159/fa89311b64d7/41588_2022_1089_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a43a/9279159/d587a765eae5/41588_2022_1089_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a43a/9279159/76115ce74aa4/41588_2022_1089_Fig10_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a43a/9279159/255ac226db26/41588_2022_1089_Fig11_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a43a/9279159/43b32b7295fc/41588_2022_1089_Fig12_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a43a/9279159/d60504f7540f/41588_2022_1089_Fig13_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a43a/9279159/fbb4318c8f0b/41588_2022_1089_Fig14_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a43a/9279159/d65e3d031df1/41588_2022_1089_Fig15_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a43a/9279159/7517cb780db6/41588_2022_1089_Fig16_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a43a/9279159/f42c31e5edf2/41588_2022_1089_Fig17_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a43a/9279159/f61734823827/41588_2022_1089_Fig18_ESM.jpg

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