Instituto de Fisiología Celular, Departaménto de Genética Molecular, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico.
Instituto de Fisiología Celular, Unidad de Bioinformática y Manejo de la Información, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico.
Genes (Basel). 2024 Apr 25;15(5):549. doi: 10.3390/genes15050549.
Recent evidence suggests that human gene promoters display gene expression regulatory mechanisms beyond the typical single gene local transcription modulation. In mammalian genomes, genes with an associated bidirectional promoter are abundant; bidirectional promoter architecture serves as a regulatory hub for a gene pair expression. However, it has been suggested that its contribution to transcriptional regulation might exceed local transcription initiation modulation. Despite their abundance, the functional consequences of bidirectional promoter architecture remain largely unexplored. This work studies the long-range gene expression regulatory role of a long non-coding RNA gene promoter using chromosome conformation capture methods. We found that this particular bidirectional promoter contributes to distal gene expression regulation in a target-specific manner by establishing promoter-promoter interactions. In particular, we validated that the promoter-promoter interactions of this regulatory element with the promoter of distal gene contribute to modulating the transcription rate of this gene; removing the bidirectional promoter from its genomic context leads to a rearrangement of promoter-enhancer interactions and to increased gene expression. Moreover, long-range regulatory functionality is not directly dependent on its associated non-coding gene pair expression levels.
最近的证据表明，人类基因启动子除了典型的单个基因局部转录调节外，还显示出基因表达的调节机制。在哺乳动物基因组中，具有相关双向启动子的基因是丰富的；双向启动子结构作为一对基因表达的调控中心。然而，有人认为它对转录调控的贡献可能超出了局部转录起始调节。尽管它们很丰富，但双向启动子结构的功能后果在很大程度上仍未得到探索。这项工作使用染色体构象捕获方法研究了长非编码 RNA 基因启动子的长程基因表达调控作用。我们发现，这个特定的双向启动子通过建立启动子-启动子相互作用，以特定于靶标的方式促进远端基因表达调控。具体来说，我们验证了该调节元件与远端基因启动子的启动子-启动子相互作用有助于调节该基因的转录速率；从其基因组环境中去除双向启动子会导致启动子-增强子相互作用的重新排列，并导致基因表达增加。此外，长程调控功能并不直接依赖于其相关的非编码基因对表达水平。
