Multi-species annotation of transcriptome and chromatin structure in domesticated animals
Multi-species annotation of transcriptome and chromatin structure in domesticated animals
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DOI：
10.1186/s12915-019-0726-5
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发表时间：
2019-12-30
期刊：
影响因子：
5.4
通讯作者：
Giuffra, Elisabetta
中科院分区：
文献类型：
--
作者：
Foissac, Sylvain;Djebali, Sarah;Giuffra, Elisabetta
背景比较基因组学研究是识别与复杂性状相关的编码和非编码元件的核心，而基因组的功能注释是破译家畜基因-表型关系的关键步骤。作为动物基因组功能注释(FAANG)行动的一部分，FR-AgENCODE项目旨在通过使用与新陈代谢(肝脏)和免疫(CD4+和CD8+T细胞)相关的三个目标样本，在代表反刍动物(牛、山羊)、单胃动物(猪)和鸟类(鸡)的物种中描绘转录环境(RNA-seq)、染色质可及性(atac-seq)和构象(Hi-C)，从而创建家养动物的参考功能图谱。结果RNA-seq分析大大扩展了现有的注释转录本目录，并发现了功能未知的差异表达基因，包括新的共线LncRNAs。ATAC-SEQ强调了在染色质的不同可达区域中转录因子结合位点的丰富。比较分析揭示了一组跨物种的保守调节区的核心集合。由Hi-C数据注释的拓扑相关结构域(TADS)和表观遗传A/B区段与RNA-seq和ATAC-seq数据一致。多物种比较表明，保守的TAD边界比物种特有的边界具有更强的绝缘特性，并且A/B区段中的同源基因的基因组分布在物种之间显著保守。结论我们报道了FAANG项目获得的第一个多物种和多分析的基因组注释结果。除了参考注释的生成和先前在模式动物上的发现的确认外，对来自多个分析和物种的数据的综合分析揭示了从鸟类到哺乳动物的多尺度选择性压力塑造基因组组织的新曙光。总体而言，这些结果强调了FAANG对家养动物研究的价值，并加强了未来对该社区生成的关于不同物种的参考数据集进行荟萃分析的重要性。
Background Comparative genomics studies are central in identifying the coding and non-coding elements associated with complex traits, and the functional annotation of genomes is a critical step to decipher the genotype-to-phenotype relationships in livestock animals. As part of the Functional Annotation of Animal Genomes (FAANG) action, the FR-AgENCODE project aimed to create reference functional maps of domesticated animals by profiling the landscape of transcription (RNA-seq), chromatin accessibility (ATAC-seq) and conformation (Hi-C) in species representing ruminants (cattle, goat), monogastrics (pig) and birds (chicken), using three target samples related to metabolism (liver) and immunity (CD4+ and CD8+ T cells). Results RNA-seq assays considerably extended the available catalog of annotated transcripts and identified differentially expressed genes with unknown function, including new syntenic lncRNAs. ATAC-seq highlighted an enrichment for transcription factor binding sites in differentially accessible regions of the chromatin. Comparative analyses revealed a core set of conserved regulatory regions across species. Topologically associating domains (TADs) and epigenetic A/B compartments annotated from Hi-C data were consistent with RNA-seq and ATAC-seq data. Multi-species comparisons showed that conserved TAD boundaries had stronger insulation properties than species-specific ones and that the genomic distribution of orthologous genes in A/B compartments was significantly conserved across species. Conclusions We report the first multi-species and multi-assay genome annotation results obtained by a FAANG project. Beyond the generation of reference annotations and the confirmation of previous findings on model animals, the integrative analysis of data from multiple assays and species sheds a new light on the multi-scale selective pressure shaping genome organization from birds to mammals. Overall, these results emphasize the value of FAANG for research on domesticated animals and reinforces the importance of future meta-analyses of the reference datasets being generated by this community on different species.