Quantitative analysis and prediction of G-quadruplex forming sequences in double-stranded DNA.
G-quadruplex (GQ) is a four-stranded DNA structure that can be formed in guanine-rich sequences. GQ structures have been proposed to regulate diverse biological processes including transcription, replication, translation and telomere maintenance. Recent studies have demonstrated the existence of GQ DNA in live mammalian cells and a significant number of potential GQ forming sequences in the human genome. We present a systematic and quantitative analysis of GQ folding propensity on a large set of 438 GQ forming sequences in double-stranded DNA by integrating fluorescence measurement, single-molecule imaging and computational modeling. We find that short minimum loop length and the thymine base are two main factors that lead to high GQ folding propensity. Linear and Gaussian process regression models further validate that the GQ folding potential can be predicted with high accuracy based on the loop length distribution and the nucleotide content of the loop sequences. Our study provides important new parameters that can inform the evaluation and classification of putative GQ sequences in the human genome.
Department of Electrical and Computer Engineering, University of Illinois; 306 N. Wright St. Urbana, IL 61801, USA Institute for Genomic Biology; 1206 Gregory Drive, Urbana, IL 61801, USA.
Minji
M
Kim
Department of Bioengineering, University of Illinois; 1304 W. Springfield Ave. Urbana, IL 61801, USA.
Alex
A
Kreig
Department of Biophysics, Johns Hopkins University; 3400 N. Charles St. Baltimore, MD 21218 USA.
Chun-Ying
CY
Lee
Institute for Genomic Biology; 1206 Gregory Drive, Urbana, IL 61801, USA Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
H Tomas
HT
Rube
Department of Bioengineering, University of Illinois; 1304 W. Springfield Ave. Urbana, IL 61801, USA School of Mathematics, University of Bristol; University Walk, Bristol BS8 1TW, UK.
Jacob
J
Calvert
Institute for Genomic Biology; 1206 Gregory Drive, Urbana, IL 61801, USA Department of Bioengineering, University of Illinois; 1304 W. Springfield Ave. Urbana, IL 61801, USA Department of Physics, University of Illinois; 1110 West Green Street, Urbana, IL 61801-3080, USA Physics Frontier Center (Center for Physics of Living Cells), University of Illinois, 1110 W. Green St. Urbana, IL 61801, USA songj@illinois.edu.
Jun S
JS
Song
Institute for Genomic Biology; 1206 Gregory Drive, Urbana, IL 61801, USA Department of Bioengineering, University of Illinois; 1304 W. Springfield Ave. Urbana, IL 61801, USA Department of Biophysics, Johns Hopkins University; 3400 N. Charles St. Baltimore, MD 21218 USA Physics Frontier Center (Center for Physics of Living Cells), University of Illinois, 1110 W. Green St. Urbana, IL 61801, USA smyong@jhu.edu.
Sua
S
Myong
D001482:Base Composition; D001483:Base Sequence; D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D016014:Linear Models; D013941:Thymine / Q000737:chemistry
D004247:DNA; D013941:Thymine