G-四链体是人类染色质中转录因子的结合中心。

G-quadruplexes are transcription factor binding hubs in human chromatin.

机构信息

Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK.

Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK.

出版信息

Genome Biol. 2021 Apr 23;22(1):117. doi: 10.1186/s13059-021-02324-z.

BACKGROUND

The binding of transcription factors (TF) to genomic targets is critical in the regulation of gene expression. Short, double-stranded DNA sequence motifs are routinely implicated in TF recruitment, but many questions remain on how binding site specificity is governed.

RESULTS

Herein, we reveal a previously unappreciated role for DNA secondary structures as key features for TF recruitment. In a systematic, genome-wide study, we discover that endogenous G-quadruplex secondary structures (G4s) are prevalent TF binding sites in human chromatin. Certain TFs bind G4s with affinities comparable to double-stranded DNA targets. We demonstrate that, in a chromatin context, this binding interaction is competed out with a small molecule. Notably, endogenous G4s are prominent binding sites for a large number of TFs, particularly at promoters of highly expressed genes.

CONCLUSIONS

Our results reveal a novel non-canonical mechanism for TF binding whereby G4s operate as common binding hubs for many different TFs to promote increased transcription.

背景

转录因子（TF）与基因组靶标的结合对于基因表达的调控至关重要。短的双链 DNA 序列基序通常与 TF 的招募有关，但关于结合位点特异性如何调控的问题仍然存在。

结果

本文揭示了 DNA 二级结构作为 TF 招募关键特征的先前未被认识到的作用。在一项系统的全基因组研究中，我们发现在人类染色质中，内源性 G-四链体二级结构（G4s）是常见的 TF 结合位点。某些 TF 与 G4s 的结合亲和力可与双链 DNA 靶标相媲美。我们证明，在染色质环境中，这种结合相互作用可被小分子竞争掉。值得注意的是，内源性 G4s 是大量 TF 的突出结合位点，尤其是在高表达基因的启动子处。