DNA G-quadruplex formation in response to remote downstream transcription activity: long-range sensing and signal transducing in DNA double helix

C Zhang,Z Tan,H.-H Liu,Y.-H Hao,K.-W Zheng

doi:10.1093/nar/gkt443

C Zhang, Z Tan + Show 3 more

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https://doi.org/10.1093/nar/gkt443

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Abstract

G-quadruplexes, four-stranded structures formed by Guanine-rich nucleic acids, are implicated in many physiological and pathological processes. G-quadruplex-forming sequences are abundant in genomic DNA, and G-quadruplexes have recently been shown to exist in the genome of mammalian cells. However, how G-quadruplexes are formed in the genomes remains largely unclear. Here, we show that G-quadruplex formation can be remotely induced by downstream transcription events that are thousands of base pairs away. The induced G-quadruplexes alter protein recognition and cause transcription termination at the local region. These results suggest that a G-quadruplex-forming sequence can serve as a sensor or receiver to sense remote DNA tracking activity in response to the propagation of mechanical torsion in a DNA double helix. We propose that the G-quadruplex formation may provide a mean for long-range sensing and communication between distal genomic locations to coordinate regulatory transactions in genomic DNA.

Highlights

Transcription is controlled by proximal promoter and distal regulatory elements in genomic DNA in the upstream region of transcription start sites (TSS)
The construct was transformed into Escherichia coli JM109 (TransGen Biotech, China), and the resulting plasmid was purified and used as template to obtain the doublestranded DNA (dsDNA) of different sizes spanning the insert by PCR (Supplementary Figure S1A)
Transcription was initiated by supplying T7 polymerase and the four nucleoside triphosphates (NTPs) in a solution containing 40% polyethylene glycol (PEG) 200 and 50 mM of K+ or Li+

Summary

Introduction

Transcription is controlled by proximal promoter and distal regulatory elements in genomic DNA in the upstream region of transcription start sites (TSS). Transcription-generated supercoiling can propagate over long distance in linear doublestranded DNA (dsDNA) in vitro [11] and in chromosomes in vivo [12]. This supercoiling propagation dynamically melts the far upstream element of human MYC gene into single-stranded DNA and subsequently permits binding of the far upstream element-binding protein. These observations demonstrate that transcription induced mechanical stress can be transmitted to remote loci along a DNA double helix

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