A comparative analysis of chromatin accessibility in cattle, pig, and mouse tissues.

A comparative analysis of chromatin accessibility in cattle, pig, and mouse tissues.
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DOI:
10.1186/s12864-020-07078-9
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发表时间:
2020-10-07
期刊:
影响因子:
4.4
通讯作者:
Ross PJ
Ross PJ
中科院分区:
生物学2区
文献类型:
--
作者:
Halstead MM;Kern C;Saelao P;Wang Y;Chanthavixay G;Medrano JF;Van Eenennaam AL;Korf I;Tuggle CK;Ernst CW;Zhou H;Ross PJ

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尽管在人类和小鼠基因组的非编码部分的注释方面取得了相当大的进展,但其他物种(如牲畜)的调控元件的特征仍然很差。这种功能注释的缺乏对农业研究构成了实质性的障碍,并降低了这些物种作为模式生物的价值。由于活性调控元件通常以染色质可及性为特征,我们实施了转座酶可及性染色质测定(ATAC-seq)来注释和表征猪和牛的调控元件,给定一组8个成年组织。总体而言,在猪和牛中分别鉴定出306,304和273,594个有效调控元件。71,478个猪和47,454个牛的调控元件具有高度的组织特异性,并相应地丰富了已知组织特异性转录因子的结合基序。然而,在每个组织中,最普遍的可接近基序对应于绝缘体CTCF,这表明普遍参与3-D染色质组织。利用类似的小鼠数据集,比较了猪、牛和小鼠的开放染色质,揭示了调控元件在序列一致性和可及性方面的保守性与进化距离一致;猪和牛共享约20%的可访问地点,而老鼠和有蹄类动物只有约10%的可访问地点是共同的。此外,可达性的保护在启动子区域比在基因间区域更为普遍。远端元件缺乏保守的可及性与增强子的快速进化是一致的,这进一步强调了对单个物种的调控元件进行注释的必要性,而不是基于同源性来推断元件。牛和猪的染色质可及性图谱是对牲畜基因组进行注释和剖析基因组与表型之间调控联系的重要一步。
Although considerable progress has been made towards annotating the noncoding portion of the human and mouse genomes, regulatory elements in other species, such as livestock, remain poorly characterized. This lack of functional annotation poses a substantial roadblock to agricultural research and diminishes the value of these species as model organisms. As active regulatory elements are typically characterized by chromatin accessibility, we implemented the Assay for Transposase Accessible Chromatin (ATAC-seq) to annotate and characterize regulatory elements in pigs and cattle, given a set of eight adult tissues. Overall, 306,304 and 273,594 active regulatory elements were identified in pig and cattle, respectively. 71,478 porcine and 47,454 bovine regulatory elements were highly tissue-specific and were correspondingly enriched for binding motifs of known tissue-specific transcription factors. However, in every tissue the most prevalent accessible motif corresponded to the insulator CTCF, suggesting pervasive involvement in 3-D chromatin organization. Taking advantage of a similar dataset in mouse, open chromatin in pig, cattle, and mice were compared, revealing that the conservation of regulatory elements, in terms of sequence identity and accessibility, was consistent with evolutionary distance; whereas pig and cattle shared about 20% of accessible sites, mice and ungulates only had about 10% of accessible sites in common. Furthermore, conservation of accessibility was more prevalent at promoters than at intergenic regions. The lack of conserved accessibility at distal elements is consistent with rapid evolution of enhancers, and further emphasizes the need to annotate regulatory elements in individual species, rather than inferring elements based on homology. This atlas of chromatin accessibility in cattle and pig constitutes a substantial step towards annotating livestock genomes and dissecting the regulatory link between genome and phenome.
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期刊: PLOS GENETICS
影响因子: 4.5
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DOI: 10.1038/s41598-020-61678-9
发表时间: 2020-03-23
期刊: SCIENTIFIC REPORTS
影响因子: 4.6
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