A unified approach for quantifying and interpreting DNA shape readout by transcription factors

Molecular Systems Biology
H Tomas RubeHarmen J Bussemaker

Abstract

Transcription factors (TFs) interpret DNA sequence by probing the chemical and structural properties of the nucleotide polymer. DNA shape is thought to enable a parsimonious representation of dependencies between nucleotide positions. Here, we propose a unified mathematical representation of the DNA sequence dependence of shape and TF binding, respectively, which simplifies and enhances analysis of shape readout. First, we demonstrate that linear models based on mononucleotide features alone account for 60-70% of the variance in minor groove width, roll, helix twist, and propeller twist. This explains why simple scoring matrices that ignore all dependencies between nucleotide positions can partially account for DNA shape readout by a TF Adding dinucleotide features as sequence-to-shape predictors to our model, we can almost perfectly explain the shape parameters. Building on this observation, we developed a post hoc analysis method that can be used to analyze any mechanism-agnostic protein-DNA binding model in terms of shape readout. Our insights provide an alternative strategy for using DNA shape information to enhance our understanding of how cis-regulatory codes are interpreted by the cellular machinery.

References

Oct 25, 1982·Journal of Molecular Biology·C R Calladine
Sep 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·W K OlsonV B Zhurkin
May 17, 2000·Bioinformatics·G D Stormo
Jul 5, 2001·Proceedings of the National Academy of Sciences of the United States of America·J HizverZ Shakked
Oct 17, 2001·Journal of Molecular Biology·W K OlsonH M Berman
Jan 10, 2003·Nucleic Acids Research·V MatysE Wingender
Jan 24, 2004·Proceedings of the National Academy of Sciences of the United States of America·Richard SteflJuli Feigon
Jan 13, 2006·Journal of Molecular Biology·Jamie M Baird-TitusMark Rance
Jan 16, 2007·Science·Sebastian J Maerkl, Stephen R Quake
Jun 11, 2009·Quarterly Reviews of Biophysics·Tali E Haran, Udayan Mohanty
Oct 30, 2009·Nature·Remo RohsBarry Honig
Dec 10, 2009·PLoS Computational Biology·Yue ZhaoGary D Stormo
Mar 26, 2010·Annual Review of Biochemistry·Remo RohsRichard S Mann
Jan 29, 2013·Nature Biotechnology·Matthew T WeirauchTimothy R Hughes
May 11, 2013·Nucleic Acids Research·Stephen P HancockReid C Johnson
Nov 26, 2013·Nucleic Acids Research·Shula ShazmanBarry Honig
Mar 17, 2015·Proceedings of the National Academy of Sciences of the United States of America·Tianyin ZhouRemo Rohs
Apr 7, 2015·Cell·Namiko AbeRichard S Mann
Jul 28, 2015·Nature Biotechnology·Babak AlipanahiBrendan J Frey
Jun 4, 2016·Nucleic Acids Research·Pei-Chen Peng, Saurabh Sinha
Aug 23, 2016·Cell Systems·Anthony MathelierWyeth W Wasserman
Jan 17, 2017·Nature Methods·Alina IsakovaBart Deplancke
Apr 6, 2017·Bioinformatics·Shuxiang RuanGary D Stormo
May 26, 2017·Bioinformatics·Wenxiu MaWilliam Stafford Noble

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Citations

Aug 8, 2018·Nucleic Acids Research·Daniel M CohenDavid J Steger
Nov 6, 2018·Nucleic Acids Research·Venkata Rajesh YellaManju Bansal
Aug 18, 2020·Computational and Structural Biotechnology Journal·Gergely Nagy, Laszlo Nagy
Nov 10, 2020·IScience·Max SchnepfUlrike Gaul
Jul 24, 2021·Organic & Biomolecular Chemistry·Alberto Mills, Federico Gago
Jul 10, 2019·Annual Review of Cell and Developmental Biology·Judith F KribelbauerRichard S Mann

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Methods Mentioned

BETA
SELEX
NMR

Software Mentioned

UniPROBE
sampleSequences
HelT
DNAshape
UbxIVa
Scr
PBM
No Read Left Behind ( NRLB )
randomKmerTable
BP

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