
Insertion of an array of G-quadruplex (G4) DNA structures into chromatin directly induces long-range chromosomal interactions and enhancer-like epigenetic changes, leading to activation of genes up to 5 Mb away.


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Although the role of G-quadruplex (G4) DNA structures has been suggested in chromosomal looping this was not tested directly. Here, to test causal function, an array of G4s, or control sequence that does not form G4s, were inserted within chromatin in cells. Compared to the control insert, we observed a remarkable increase in the number of 3D chromatin looping interactions from the inserted G4 array. This was evident within the immediate topologically associated domain (TAD) and throughout the genome. Locally, recruitment of enhancer histone marks and the transcriptional coactivator p300/Acetylated-p300 increased in the G4-array, but not in the control insertion. Resulting promoter-enhancer interactions and gene activation were clear up to 5 Mb away from the insertion site. Together, these show the causal role of G4s in enhancer function and long-range chromatin interactions. Mechanisms of 3D topology are primarily based on DNA-bound architectural proteins that induce/stabilize long-range interactions. Involvement of the underlying intrinsic DNA sequence/structure in 3D looping shown here therefore throws new light on how long-range chromosomal interactions might be induced or maintained.

### Competing Interest Statement

The authors have declared no competing interest.

The sequencing data underlying this article are available in the NCBI Sequence Read Archive, scheduled to be released upon publication and would be accessible using the following link-<https://www.ncbi.nlm.nih.gov/sra/?term=PRJNA1048044>. The rest of the data are available in the article and its online supplementary material. Further inquiries can be directed to the corresponding author.

Artificially inserted G-quadruplex DNA secondary structures induce long-distance chromatin activation

insertion-of-g-quadruplex-dna-structures-induces-long-range-chromatin-activation-and-gene-expression


Insertion of G-quadruplex DNA Structures Induces Long-Range Chromatin Activation and Gene Expression
