CSIRO Agriculture & Food, 306 Carmody Rd., QLD, 4067, Brisbane, Australia.
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.
Genome Biol. 2021 Sep 21;22(1):273. doi: 10.1186/s13059-021-02489-7.
Spatiotemporal changes in the chromatin accessibility landscape are essential to cell differentiation, development, health, and disease. The quest of identifying regulatory elements in open chromatin regions across different tissues and developmental stages is led by large international collaborative efforts mostly focusing on model organisms, such as ENCODE. Recently, the Functional Annotation of Animal Genomes (FAANG) has been established to unravel the regulatory elements in non-model organisms, including cattle. Now, we can transition from prediction to validation by experimentally identifying the regulatory elements in tropical indicine cattle. The identification of regulatory elements, their annotation and comparison with the taurine counterpart, holds high promise to link regulatory regions to adaptability traits and improve animal productivity and welfare.
We generate open chromatin profiles for liver, muscle, and hypothalamus of indicine cattle through ATAC-seq. Using robust methods for motif discovery, motif enrichment and transcription factor binding sites, we identify potential master regulators of the epigenomic profile in these three tissues, namely HNF4, MEF2, and SOX factors, respectively. Integration with transcriptomic data allows us to confirm some of their target genes. Finally, by comparing our results with Bos taurus data we identify potential indicine-specific open chromatin regions and overlaps with indicine selective sweeps.
Our findings provide insights into the identification and analysis of regulatory elements in non-model organisms, the evolution of regulatory elements within two cattle subspecies as well as having an immediate impact on the animal genetics community in particular for a relevant productive species such as tropical cattle.
染色质可及性景观的时空变化对于细胞分化、发育、健康和疾病至关重要。在不同组织和发育阶段的开放染色质区域中识别调控元件的探索,主要由专注于模式生物的大型国际合作努力引领,如 ENCODE。最近,功能注释动物基因组(FAANG)已经建立,以揭示非模式生物(包括牛)中的调控元件。现在,我们可以通过实验鉴定热带亚洲野牛中的调控元件,从预测转向验证。调控元件的鉴定、注释及其与 Taurine 对应物的比较,有望将调控区域与适应性特征联系起来,提高动物的生产力和福利。
我们通过 ATAC-seq 为亚洲野牛的肝脏、肌肉和下丘脑生成了开放染色质图谱。通过使用稳健的方法进行基序发现、基序富集和转录因子结合位点分析,我们分别鉴定了这三种组织中表观基因组图谱的潜在主调控因子,即 HNF4、MEF2 和 SOX 因子。与转录组数据的整合使我们能够确认其中一些靶基因。最后,通过将我们的结果与 Bos taurus 数据进行比较,我们确定了潜在的亚洲野牛特异性开放染色质区域和与亚洲野牛选择清除的重叠。
我们的研究结果为非模式生物中调控元件的识别和分析提供了见解,揭示了两个牛亚种内调控元件的进化,以及对动物遗传学社区特别是对热带牛等相关生产物种的直接影响。