Characterizing transcription start sites is essential for understanding the regulatory mechanisms that control gene expression. Recently, a new bovine genome assembly (ARS-UCD1.2) with high continuity, accuracy, and completeness was released; however, the functional annotation of the bovine genome lacks precise transcription start sites and contains a low number of transcripts in comparison to human and mouse. Using the RAMPAGE approach, this study identified transcription start sites at high resolution in a large collection of bovine tissues. We found several known and novel transcription start sites attributed to promoters of protein coding and lncRNA genes that were validated through experimental and in silico evidence. With these findings, the annotation of transcription start sites in cattle reached a level comparable to the mouse and human genome annotations. In addition, we identified and characterized transcription start sites for antisense transcripts derived from bidirectional promoters, potential lncRNAs, mRNAs, and pre-miRNAs. We also analyzed the quantitative aspects of RAMPAGE to produce a promoter activity atlas, reaching highly reproducible results comparable to traditional RNA-seq. Co-expression networks revealed considerable use of tissue specific promoters, especially between brain and testicle, which expressed several genes in common from alternate loci. Furthermore, regions surrounding co-expressed modules were enriched in binding factor motifs representative of each tissue. The comprehensive annotation of promoters in such a large collection of tissues will substantially contribute to our understanding of gene expression in cattle and other mammalian species, shortening the gap between genotypes and phenotypes.

中文翻译：

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在31个牛组织中的转录起始图谱揭示了复杂的启动子活性，普遍的转录和组织特异性启动子的使用

表征转录起始位点对于理解控制基因表达的调控机制至关重要。最近，发布了一种具有高度连续性，准确性和完整性的新型牛基因组装配体（ARS-UCD1.2）；然而，与人类和小鼠相比，牛基因组的功能注释缺少精确的转录起始位点，并且包含少量的转录本。使用RAMPAGE方法，本研究在大量牛组织中以高分辨率鉴定了转录起始位点。我们发现归因于蛋白质编码和lncRNA基因启动子的几个已知和新颖的转录起始位点，这些位点已通过实验和计算机模拟得到了验证。有了这些发现，牛中转录起始位点的注释达到了与小鼠和人类基因组注释相当的水平。此外，我们鉴定和表征了来自双向启动子，潜在的lncRNA，mRNA和pre-miRNA的反义转录物的转录起始位点。我们还分析了RAMPAGE产生启动子活性图谱的定量方面，可达到与传统RNA-seq相当的可重复性结果。共表达网络揭示了组织特异性启动子的大量使用，特别是在大脑和睾丸之间，它们表达了来自其他基因座的几个共同基因。此外，共表达模块周围的区域富含代表每个组织的结合因子基序。