Institute for Chemical Reaction Design and Discovery, Hokkaido University, Kita 21, Nishi 10, Kita-ku, Sapporo 001-0021, Japan.
PRESTO, Japan Science and Technology Agency (JST), 4-1-8, Honcho, Kawaguchi, Saitama 332-0012, Japan.
Nucleic Acids Res. 2021 May 21;49(9):5017-5027. doi: 10.1093/nar/gkab275.
Enhancers are DNA sequences at a long genomic distance from target genes. Recent experiments suggest that enhancers are anchored to the surfaces of condensates of transcription machinery and that the loop extrusion process enhances the transcription level of their target genes. Here, we theoretically study the polymer dynamics driven by the loop extrusion of the linker DNA between an enhancer and the promoter of its target gene to calculate the contact probability of the promoter to the transcription machinery in the condensate. Our theory predicts that when the loop extrusion process is active, the contact probability increases with increasing linker DNA length. This finding reflects the fact that the relaxation time, with which the promoter stays in proximity to the surface of the transcriptional condensate, increases as the length of the linker DNA increases. This contrasts the equilibrium case for which the contact probability between the promoter and the transcription machineries is smaller for longer linker DNA lengths.
增强子是与靶基因在基因组上有长距离的 DNA 序列。最近的实验表明,增强子被锚定在转录机器的凝聚物的表面上,并且环挤出过程增强了其靶基因的转录水平。在这里,我们从理论上研究了由增强子和其靶基因的启动子之间的连接 DNA 的环挤出驱动的聚合物动力学,以计算启动子与凝聚物中的转录机器的接触概率。我们的理论预测,当环挤出过程活跃时,接触概率随连接 DNA 长度的增加而增加。这一发现反映了这样一个事实,即启动子与转录凝聚物表面保持接近的松弛时间随着连接 DNA 长度的增加而增加。这与平衡情况形成对比,在平衡情况下,较长的连接 DNA 长度会导致启动子与转录机器之间的接触概率更小。