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.

中文翻译：

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跨牛组织的染色质可及性和监管词汇


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。识别不同组织和发育阶段的开放染色质区域中的调控元件的探索是由主要关注模式生物的大型国际合作努力主导的，例如 ENCODE。最近，动物基因组功能注释（FAANG）已经建立，以阐明包括牛在内的非模式生物的调控元件。现在，我们可以通过实验确定热带牛的调控元件，从预测过渡到验证。调控元件的识别、它们的注释以及与牛磺酸对应物的比较，对于将调控区域与适应性特征联系起来并提高动物生产力和福利具有很大的希望。我们通过 ATAC-seq 生成 indicine 牛的肝脏、肌肉和下丘脑的开放染色质图谱。使用稳健的基序发现、基序富集和转录因子结合位点方法，我们分别确定了这三种组织中表观基因组谱的潜在主调节因子，即 HNF4、MEF2 和 SOX 因子。与转录组数据的整合使我们能够确认它们的一些目标基因。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 indicine 特异性开放染色质区域并与 indicine 选择性扫描重叠。我们的研究结果为非模式生物中调控元件的识别和分析、两个牛亚种内调控元件的进化提供了见解，并对动物遗传学界产生了直接影响，特别是对相关生产物种（如热带牛） 。