Unraveling determinants of transcription factor binding outside the core binding site

Genome Research
Michal LevoEran Segal

Abstract

Binding of transcription factors (TFs) to regulatory sequences is a pivotal step in the control of gene expression. Despite many advances in the characterization of sequence motifs recognized by TFs, our ability to quantitatively predict TF binding to different regulatory sequences is still limited. Here, we present a novel experimental assay termed BunDLE-seq that provides quantitative measurements of TF binding to thousands of fully designed sequences of 200 bp in length within a single experiment. Applying this binding assay to two yeast TFs, we demonstrate that sequences outside the core TF binding site profoundly affect TF binding. We show that TF-specific models based on the sequence or DNA shape of the regions flanking the core binding site are highly predictive of the measured differential TF binding. We further characterize the dependence of TF binding, accounting for measurements of single and co-occurring binding events, on the number and location of binding sites and on the TF concentration. Finally, by coupling our in vitro TF binding measurements, and another application of our method probing nucleosome formation, to in vivo expression measurements carried out with the same template sequences serving as promoters,...Continue Reading

References

Apr 2, 1992·Nature·R MarmorsteinS C Harrison
Dec 8, 1995·Journal of Molecular Biology·W KellerT J Richmond
Jun 1, 1961·Journal of Molecular Biology·F JACOB, J MONOD
Jan 16, 2007·Science·Sebastian J Maerkl, Stephen R Quake
Apr 18, 2007·Proceedings of the National Academy of Sciences of the United States of America·Alexandre V Morozov, Eric D Siggia
Nov 8, 2008·PLoS Computational Biology·Yair FieldEran Segal
Dec 19, 2008·Nature·Noam KaplanEran Segal
Feb 12, 2009·Current Opinion in Structural Biology·Eran Segal, Jonathan Widom
May 20, 2009·Genome Research·Tali Raveh-SadkaEran Segal
Jun 10, 2009·Nature Reviews. Genetics·Eran Segal, Jonathan Widom
Jul 22, 2009·Nature Structural & Molecular Biology·Yong ZhangKevin Struhl
Oct 30, 2009·Nature·Remo RohsBarry Honig
Mar 26, 2010·Annual Review of Biochemistry·Remo RohsRichard S Mann
Sep 17, 2010·PLoS Genetics·Michael J Guertin, John T Lis
Jun 28, 2011·Nature Biotechnology·Razvan NutiuChristopher B Burge
Dec 8, 2011·Molecular Systems Biology·Trevor SiggersMartha L Bulyk
Apr 6, 2012·PLoS Genetics·Michael J GuertinJohn T Lis
Sep 1, 2012·Annual Review of Genetics·Katherine M LelliRichard S Mann
Jan 22, 2013·Cell·Arttu JolmaJussi Taipale
Feb 16, 2013·Science·Sangjin KimX Sunney Xie
Mar 7, 2013·Nature Structural & Molecular Biology·Kevin Struhl, Eran Segal
Jul 3, 2013·Proceedings of the National Academy of Sciences of the United States of America·Michael A WhiteBarak A Cohen
Aug 21, 2013·Nature Genetics·Arun S RajkumarSebastian J Maerkl
Jun 11, 2014·Nature Reviews. Genetics·Michal Levo, Eran Segal
Aug 19, 2014·Trends in Biochemical Sciences·Matthew SlatteryRemo Rohs

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Citations

Dec 18, 2015·Seminars in Cell & Developmental Biology·Ignacio Maeso, Juan J Tena
Nov 22, 2015·Nucleic Acids Research·Liang LiuXiaobo Zhou
Apr 6, 2016·IEEE/ACM Transactions on Computational Biology and Bioinformatics·Ka-Chun WongHau-San Wong
May 20, 2016·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Iris DrorYael Mandel-Gutfreund
Jun 12, 2016·Nucleic Acids Research·Matthias Siebert, Johannes Söding
Jun 18, 2016·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·E Christopher PartridgeEric M Mendenhall
Aug 6, 2016·Nucleic Acids Research·Wenqiang ShiWyeth W Wasserman
Aug 23, 2016·Cell Systems·Anthony MathelierWyeth W Wasserman
Nov 3, 2016·DNA Research : an International Journal for Rapid Publication of Reports on Genes and Genomes·Aditya Kumar, Manju Bansal
Feb 1, 2017·Proceedings of the National Academy of Sciences of the United States of America·Sharon R GrossmanEric S Lander
Mar 28, 2017·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Slawomir KubikDavid Shore
May 26, 2017·Bioinformatics·Wenxiu MaWilliam Stafford Noble
Apr 22, 2017·Genome Biology and Evolution·Xueying C Li, Justin C Fay
Nov 23, 2017·Nucleic Acids Research·Sridevi RanganathanKathleen A McDonough
Mar 5, 2016·Integrative Biology : Quantitative Biosciences From Nano to Macro·Ben J VincentAngela H DePace
Aug 16, 2017·Physical Chemistry Chemical Physics : PCCP·Anna Ochab-MarcinekMarcin Tabaka
Apr 21, 2018·Evolution; International Journal of Organic Evolution·José Aguilar-RodríguezJoshua L Payne
Aug 8, 2018·Nucleic Acids Research·Daniel M CohenDavid J Steger
Nov 6, 2018·Nucleic Acids Research·Venkata Rajesh YellaManju Bansal
Feb 5, 2019·PLoS Computational Biology·Stephanie L BarnesRob Phillips
May 12, 2020·Briefings in Bioinformatics·Xiaohui NiuXuehai Hu
Mar 24, 2017·Human Molecular Genetics·Giuseppe GalloneAntonio J Berlanga-Taylor
Jan 19, 2019·Molecular Biology and Evolution·Xiao Yi, Antony M Dean
Aug 9, 2016·Briefings in Functional Genomics·Yaron Orenstein, Ron Shamir
Jun 6, 2017·Nature Communications·Sivakanthan KasinathanSteven Henikoff
Jun 14, 2017·Scientific Reports·Hongbo ZhangDe-Shuang Huang
Mar 29, 2018·Proceedings of the National Academy of Sciences of the United States of America·Daniel D LePolly M Fordyce
Mar 9, 2019·Frontiers in Plant Science·Dinusha C MaheepalaAmy Litt
Jan 21, 2018·Nature Communications·Kyle A CottrellSergej Djuranovic

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