斑馬魚順式調控元件和三維基因組結構圖獲解析
作者：
小柯機器人發布時間：2020/11/27 13:16:25
2020年11月25日出版的《自然》雜誌在線發表了美國西北大學嶽峰課題組的最新研究成果。他們的研究揭示了斑馬魚（Danio rerio）的順式調控元件和3D基因組結構圖。
在本研究中，研究人員進行了RNA測序、利用測序（ATAC-seq）對轉座酶染色質的可及性進行了測定，並通過染色質免疫沉澱、全基因組亞硫酸氫鹽測序和染色體構象捕獲（Hi-C）實驗生成了Tu?bingen 品系斑馬魚11個成年組織和2個胚胎組織的組織特異性轉錄組、順式調控元件、異染色質、甲基化和3D基因組的綜合圖譜。通過比較斑馬魚、人和小鼠的調控元件，研究人員鑑定了進化上保守的物種特異性調控序列和網絡。研究人員觀察到進化斷點在拓撲關聯域邊界的富集，這與組蛋白H3賴氨酸4三甲基化（H3K4me3）和CCCTC結合因子（CTCF）信號強度相關。
研究人員對斑馬魚的大腦進行了單細胞ATAC-seq，揭示了25種不同的細胞類型簇。通過結合長時間閱讀DNA測序和Hi-C，研究人員重構了決定性別的4條從頭合成染色體。總體而言，該工作為脊椎動物基因組的功能注釋和3D基因組保守進化元素的研究提供了附加的表觀基因組圖。
據介紹，斑馬魚已被廣泛用於研究人類發育和疾病進展，並且約有70％的蛋白質編碼基因在兩個物種之間是保守的。然而，對斑馬魚的研究仍然受到對斑馬魚基因組中功能調控元件理解的限制。
附：英文原文
Title: A map of cis -regulatory elements and 3D genome structures in zebrafish
Author: 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, Feng Yue
Issue&Volume: 2020-11-25
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. A comprehensive map of transcriptomes, cis-regulatory elements, heterochromatin structure, the methylome and 3D genome organization in the zebrafish (Danio rerio) enables identification of species-specific and evolutionarily conserved regulatory features, and provides a foundation for modelling studies on human disease and development.
DOI: 10.1038/s41586-020-2962-9
Source: https://www.nature.com/articles/s41586-020-2962-9