Biofisika Institute (CSIC, UPV/EHU), University of the Basque Country (UPV/EHU), P.O. Box 644, 48080, Bilbao, Spain.
IKERBASQUE, Basque Foundation for Science, 48011, Bilbao, Spain.
Sci Rep. 2023 Jul 5;13(1):10835. doi: 10.1038/s41598-023-37140-x.
The prevalent one-dimensional alignment of genomic signals to a reference landmark is a cornerstone of current methods to study transcription and its DNA-dependent processes but it is prone to mask potential relations among multiple DNA elements. We developed a systematic approach to align genomic signals to multiple locations simultaneously by expanding the dimensionality of the genomic-coordinate space. We analyzed transcription in human and uncovered a complex dependence on the relative position of neighboring transcription start sites (TSSs) that is consistently conserved among cell types. The dependence ranges from enhancement to suppression of transcription depending on the relative distances to the TSSs, their intragenic position, and the transcriptional activity of the gene. Our results reveal a conserved hierarchy of alternative TSS usage within a previously unrecognized level of genomic organization and provide a general methodology to analyze complex functional relationships among multiple types of DNA elements.
目前研究转录及其 DNA 依赖性过程的方法主要是将基因组信号沿一维方向与参考标志对齐，但是这种方法容易掩盖多个 DNA 元件之间的潜在关系。我们开发了一种系统的方法，可以通过扩展基因组坐标空间的维度，同时将基因组信号对齐到多个位置。我们在人类中分析了转录，发现转录与相邻转录起始位点 (TSS) 的相对位置之间存在复杂的依赖性，这种依赖性在细胞类型之间是一致保守的。这种依赖性的范围从增强到抑制转录，具体取决于与 TSS 的相对距离、它们在基因内的位置以及基因的转录活性。我们的结果揭示了在以前未被认识到的基因组组织水平内，替代 TSS 使用的一种保守层次结构，并提供了一种分析多种类型 DNA 元件之间复杂功能关系的通用方法。
