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朱晓宁, 王宇哲, 李冲, 吴寒宇, 张然, 胡晓湘. 2023: 鸡染色质可及性图谱加速了鸟类的表观遗传注释和生长性状相关的基因精细定位. 动物学研究, 44(1): 53-62. DOI: 10.24272/j.issn.2095-8137.2022.228
引用本文: 朱晓宁, 王宇哲, 李冲, 吴寒宇, 张然, 胡晓湘. 2023: 鸡染色质可及性图谱加速了鸟类的表观遗传注释和生长性状相关的基因精细定位. 动物学研究, 44(1): 53-62. DOI: 10.24272/j.issn.2095-8137.2022.228
Xiao-Ning Zhu, Yu-Zhe Wang, Chong Li, Han-Yu Wu, Ran Zhang, Xiao-Xiang Hu. 2023: Chicken chromatin accessibility atlas accelerates epigenetic annotation of birds and gene fine-mapping associated with growth traits. Zoological Research, 44(1): 53-62. DOI: 10.24272/j.issn.2095-8137.2022.228
Citation: Xiao-Ning Zhu, Yu-Zhe Wang, Chong Li, Han-Yu Wu, Ran Zhang, Xiao-Xiang Hu. 2023: Chicken chromatin accessibility atlas accelerates epigenetic annotation of birds and gene fine-mapping associated with growth traits. Zoological Research, 44(1): 53-62. DOI: 10.24272/j.issn.2095-8137.2022.228

鸡染色质可及性图谱加速了鸟类的表观遗传注释和生长性状相关的基因精细定位

Chicken chromatin accessibility atlas accelerates epigenetic annotation of birds and gene fine-mapping associated with growth traits

  • 摘要: ENCODE等人类表观基因组图谱的建立,为基因调控研究提供了资源,也为疾病相关调控元件的研究提供了参考。然而目前鸟类中的表观注释信息,例如鸟类特异性染色质可及性图谱,依然较为缺乏。内含子和基因间区较短是鸟类与哺乳动物基因组的主要区别,这不利于根据已有人类或小鼠的表观基因组图谱来研究鸟类调控区域的功能。该研究以鸡作为鸟类的模式动物,利用11个组织的53个ATAC-seq样本系统地建立了鸡染色质可及性图谱。每个样本平均鉴定出50 796个染色质可及性峰,累积占鸡基因组的20.36%。染色质可及性峰的组织特异性主要反映在基因间区和内含子区,并通过(1)招募序列特异性转录因子和(2)直接调节相邻的功能基因这两种机制实现基因特定功能的调节。通过进一步整合全基因组关联分析数据,发现鸡的体重是由在多个生长发育相关组织的多个功能基因共同影响的,其中CAB39L(活跃于十二指肠)、RCBTB1(肌肉和肝脏)和新lncRNA ENSGALG00000053256(骨骼)是调节鸡体重的重要候选基因。综上,该研究证明了表观遗传图谱在精细定位功能突变中的作用,并为进一步研究鸟类和哺乳动物的表观遗传和进化基因组学提供了重要资源。

     

    Abstract: The development of epigenetic maps, such as the ENCODE project in humans, provides resources for gene regulation studies and a reference for research of disease-related regulatory elements. However, epigenetic information, such as a bird-specific chromatin accessibility atlas, is currently lacking for the thousands of bird species currently described. The major genomic difference between birds and mammals is their shorter introns and intergenic distances, which seriously hinders the use of humans and mice as a reference for studying the function of important regulatory regions in birds. In this study, using chicken as a model bird species, we systematically compiled a chicken chromatin accessibility atlas using 53 Assay of Transposase Accessible Chromatin sequencing (ATAC-seq) samples across 11 tissues. An average of 50 796 open chromatin regions were identified per sample, cumulatively accounting for 20.36% of the chicken genome. Tissue specificity was largely reflected by differences in intergenic and intronic peaks, with specific functional regulation achieved by two mechanisms: recruitment of several sequence-specific transcription factors and direct regulation of adjacent functional genes. By integrating data from genome-wide association studies, our results suggest that chicken body weight is driven by different regulatory variants active in growth-relevant tissues. We propose CAB39L (active in the duodenum), RCBTB1 (muscle and liver), and novel long non-coding RNA ENSGALG00000053256 (bone) as candidate genes regulating chicken body weight. Overall, this study demonstrates the value of epigenetic data in fine-mapping functional variants and provides a compendium of resources for further research on the epigenetics and evolution of birds and mammals.

     

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