Center for Applied Bioinformatics, St. Jude Children's Research Hospital, Memphis, TN, USA.
Institute of Human Biology and Evolution, Faculty of Biology, Adam Mickiewicz University, Poznań, Poland.
Sci Rep. 2021 Apr 26;11(1):8984. doi: 10.1038/s41598-021-87970-w.
Despite the number of studies focused on sense-antisense transcription, the key question of whether such organization evolved as a regulator of gene expression or if this is only a byproduct of other regulatory processes has not been elucidated to date. In this study, protein-coding sense-antisense gene pairs were analyzed with a particular focus on pairs overlapping at their 5' ends. Analyses were performed in 73 human transcription start site libraries. The results of our studies showed that the overlap between genes is not a stable feature and depends on which TSSs are utilized in a given cell type. An analysis of gene expression did not confirm that overlap between genes causes downregulation of their expression. This observation contradicts earlier findings. In addition, we showed that the switch from one promoter to another, leading to genes overlap, may occur in response to changing environment of a cell or tissue. We also demonstrated that in transfected and cancerous cells genes overlap is observed more often in comparison with normal tissues. Moreover, utilization of overlapping promoters depends on particular state of a cell and, at least in some groups of genes, is not merely coincidental.
尽管有许多研究集中在反义转录上，但到目前为止，这个关键问题仍未得到解答，即这种组织是作为基因表达的调节剂进化而来的，还是仅仅是其他调节过程的副产品。在这项研究中，我们分析了蛋白质编码的正反义基因对，特别关注那些在 5'端重叠的基因对。分析在 73 个人类转录起始位点文库中进行。我们的研究结果表明，基因之间的重叠不是一个稳定的特征，而是取决于在给定细胞类型中使用哪些 TSS。对基因表达的分析并没有证实基因之间的重叠会导致其表达下调。这一观察结果与早期的发现相矛盾。此外，我们还表明，从一个启动子切换到另一个启动子，导致基因重叠，可能是对细胞或组织环境变化的一种反应。我们还证明，在转染和癌细胞中，与正常组织相比，基因重叠更为常见。此外，重叠启动子的利用取决于细胞的特定状态，至少在某些基因群中，这并非偶然。
