Sequence specificity incompletely defines the genome-wide occupancy of Myc
Identifieur interne : 001A87 ( Main/Exploration ); précédent : 001A86; suivant : 001A88Sequence specificity incompletely defines the genome-wide occupancy of Myc
Auteurs : Jiannan Guo [États-Unis] ; Tiandao Li [États-Unis] ; Joshua Schipper [États-Unis] ; Kyle A. Nilson [États-Unis] ; Francis K. Fordjour [États-Unis] ; Jeffrey J. Cooper [États-Unis] ; Raluca Gordân [États-Unis] ; David H. Price [États-Unis]Source :
- Genome Biology [ 1465-6906 ] ; 2014.
Descripteurs français
- KwdFr :
- Analyse de séquence d'ADN, Facteurs de transcription à motifs basiques hélice-boucle-hélice et à glissière à leucines (), Facteurs de transcription à motifs basiques hélice-boucle-hélice et à glissière à leucines (métabolisme), Facteurs de transcription à motifs basiques hélice-boucle-hélice et à glissière à leucines (physiologie), Génome humain, Humains, Immunoprécipitation de la chromatine, Protéines proto-oncogènes c-myc (), Protéines proto-oncogènes c-myc (métabolisme), Protéines proto-oncogènes c-myc (physiologie), RNA polymerase II (métabolisme), RNA polymerase II (physiologie), Régions promotrices (génétique), Test de retard de migration électrophorétique, Transcription génétique (physiologie), Éléments E-box.
- MESH :
- métabolisme : Facteurs de transcription à motifs basiques hélice-boucle-hélice et à glissière à leucines, Protéines proto-oncogènes c-myc, RNA polymerase II.
- physiologie : Facteurs de transcription à motifs basiques hélice-boucle-hélice et à glissière à leucines, Protéines proto-oncogènes c-myc, RNA polymerase II, Transcription génétique.
- Analyse de séquence d'ADN, Facteurs de transcription à motifs basiques hélice-boucle-hélice et à glissière à leucines, Génome humain, Humains, Immunoprécipitation de la chromatine, Protéines proto-oncogènes c-myc, Régions promotrices (génétique), Test de retard de migration électrophorétique, Éléments E-box.
English descriptors
- KwdEn :
- Basic Helix-Loop-Helix Leucine Zipper Transcription Factors (chemistry), Basic Helix-Loop-Helix Leucine Zipper Transcription Factors (metabolism), Basic Helix-Loop-Helix Leucine Zipper Transcription Factors (physiology), Chromatin Immunoprecipitation, E-Box Elements, Electrophoretic Mobility Shift Assay, Genome, Human, Humans, Promoter Regions, Genetic, Proto-Oncogene Proteins c-myc (chemistry), Proto-Oncogene Proteins c-myc (metabolism), Proto-Oncogene Proteins c-myc (physiology), RNA Polymerase II (metabolism), RNA Polymerase II (physiology), Sequence Analysis, DNA, Transcription, Genetic (physiology).
- MESH :
- chemical , chemistry : Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Proto-Oncogene Proteins c-myc.
- chemical , metabolism : Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Proto-Oncogene Proteins c-myc, RNA Polymerase II.
- chemical , physiology : Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Proto-Oncogene Proteins c-myc, RNA Polymerase II.
- physiology : Transcription, Genetic.
- Chromatin Immunoprecipitation, E-Box Elements, Electrophoretic Mobility Shift Assay, Genome, Human, Humans, Promoter Regions, Genetic, Sequence Analysis, DNA.
Abstract
The Myc-Max heterodimer is a transcription factor that regulates expression of a large number of genes. Genome occupancy of Myc-Max is thought to be driven by Enhancer box (E-box) DNA elements, CACGTG or variants, to which the heterodimer binds
By analyzing ChIP-Seq datasets, we demonstrate that the positions occupied by Myc-Max across the human genome correlate with the RNA polymerase II, Pol II, transcription machinery significantly better than with E-boxes. Metagene analyses show that in promoter regions, Myc is uniformly positioned about 100 bp upstream of essentially all promoter proximal paused polymerases with Max about 15 bp upstream of Myc. We re-evaluate the DNA binding properties of full length Myc-Max proteins. Electrophoretic mobility shift assay results demonstrate Myc-Max heterodimers display significant sequence preference, but have high affinity for any DNA. Quantification of the relative affinities of Myc-Max for all possible 8-mers using universal protein-binding microarray assays shows that sequences surrounding core 6-mers significantly affect binding. Compared to the
We quantified the affinity of Myc-Max to all possible 8-mers and compared this with the sites of Myc binding across the human genome. Our results indicate that the genomic occupancy of Myc cannot be explained by its intrinsic DNA specificity and suggest that the transcription machinery and associated promoter accessibility play a predominant role in Myc recruitment.
The online version of this article (doi:10.1186/s13059-014-0482-3) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1186/s13059-014-0482-3
PubMed: 25287278
PubMed Central: 4242493
Affiliations:
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Nilson</name><affiliation wicri:level="2"><nlm:aff id="Aff2">Molecular and Cellular Biology Program, University of Iowa, Iowa City, IA 52242 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Iowa</region></placeName><wicri:cityArea>Molecular and Cellular Biology Program, University of Iowa, Iowa City</wicri:cityArea></affiliation></author><author><name sortKey="Fordjour, Francis K" sort="Fordjour, Francis K" uniqKey="Fordjour F" first="Francis K" last="Fordjour">Francis K. Fordjour</name><affiliation wicri:level="2"><nlm:aff id="Aff1">Department of Biochemistry, University of Iowa, Iowa City, IA 52242 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Iowa</region></placeName><wicri:cityArea>Department of Biochemistry, University of Iowa, Iowa City</wicri:cityArea></affiliation></author><author><name sortKey="Cooper, Jeffrey J" sort="Cooper, Jeffrey J" uniqKey="Cooper J" first="Jeffrey J" last="Cooper">Jeffrey J. Cooper</name><affiliation wicri:level="2"><nlm:aff id="Aff1">Department of Biochemistry, University of Iowa, Iowa City, IA 52242 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Iowa</region></placeName><wicri:cityArea>Department of Biochemistry, University of Iowa, Iowa City</wicri:cityArea></affiliation></author><author><name sortKey="Gordan, Raluca" sort="Gordan, Raluca" uniqKey="Gordan R" first="Raluca" last="Gordân">Raluca Gordân</name><affiliation wicri:level="2"><nlm:aff id="Aff3">Institute for Genome Sciences and Policy, Duke University, Durham, NC 27708 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Institute for Genome Sciences and Policy, Duke University, Durham</wicri:cityArea></affiliation></author><author><name sortKey="Price, David H" sort="Price, David H" uniqKey="Price D" first="David H" last="Price">David H. Price</name><affiliation wicri:level="2"><nlm:aff id="Aff1">Department of Biochemistry, University of Iowa, Iowa City, IA 52242 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Iowa</region></placeName><wicri:cityArea>Department of Biochemistry, University of Iowa, Iowa City</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="Aff2">Molecular and Cellular Biology Program, University of Iowa, Iowa City, IA 52242 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Iowa</region></placeName><wicri:cityArea>Molecular and Cellular Biology Program, University of Iowa, Iowa City</wicri:cityArea></affiliation></author></analytic><series><title level="j">Genome Biology</title><idno type="ISSN">1465-6906</idno><idno type="eISSN">1465-6914</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Basic Helix-Loop-Helix Leucine Zipper Transcription Factors (chemistry)</term><term>Basic Helix-Loop-Helix Leucine Zipper Transcription Factors (metabolism)</term><term>Basic Helix-Loop-Helix Leucine Zipper Transcription Factors (physiology)</term><term>Chromatin Immunoprecipitation</term><term>E-Box Elements</term><term>Electrophoretic Mobility Shift Assay</term><term>Genome, Human</term><term>Humans</term><term>Promoter Regions, Genetic</term><term>Proto-Oncogene Proteins c-myc (chemistry)</term><term>Proto-Oncogene Proteins c-myc (metabolism)</term><term>Proto-Oncogene Proteins c-myc (physiology)</term><term>RNA Polymerase II (metabolism)</term><term>RNA Polymerase II (physiology)</term><term>Sequence Analysis, DNA</term><term>Transcription, Genetic (physiology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Analyse de séquence d'ADN</term><term>Facteurs de transcription à motifs basiques hélice-boucle-hélice et à glissière à leucines ()</term><term>Facteurs de transcription à motifs basiques hélice-boucle-hélice et à glissière à leucines (métabolisme)</term><term>Facteurs de transcription à motifs basiques hélice-boucle-hélice et à glissière à leucines (physiologie)</term><term>Génome humain</term><term>Humains</term><term>Immunoprécipitation de la chromatine</term><term>Protéines proto-oncogènes c-myc ()</term><term>Protéines proto-oncogènes c-myc (métabolisme)</term><term>Protéines proto-oncogènes c-myc (physiologie)</term><term>RNA polymerase II (métabolisme)</term><term>RNA polymerase II (physiologie)</term><term>Régions promotrices (génétique)</term><term>Test de retard de migration électrophorétique</term><term>Transcription génétique (physiologie)</term><term>Éléments E-box</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Basic Helix-Loop-Helix Leucine Zipper Transcription Factors</term><term>Proto-Oncogene Proteins c-myc</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Basic Helix-Loop-Helix Leucine Zipper Transcription Factors</term><term>Proto-Oncogene Proteins c-myc</term><term>RNA Polymerase II</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Basic Helix-Loop-Helix Leucine Zipper Transcription Factors</term><term>Proto-Oncogene Proteins c-myc</term><term>RNA Polymerase II</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Facteurs de transcription à motifs basiques hélice-boucle-hélice et à glissière à leucines</term><term>Protéines proto-oncogènes c-myc</term><term>RNA polymerase II</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Facteurs de transcription à motifs basiques hélice-boucle-hélice et à glissière à leucines</term><term>Protéines proto-oncogènes c-myc</term><term>RNA polymerase II</term><term>Transcription génétique</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Transcription, Genetic</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Chromatin Immunoprecipitation</term><term>E-Box Elements</term><term>Electrophoretic Mobility Shift Assay</term><term>Genome, Human</term><term>Humans</term><term>Promoter Regions, Genetic</term><term>Sequence Analysis, DNA</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Analyse de séquence d'ADN</term><term>Facteurs de transcription à motifs basiques hélice-boucle-hélice et à glissière à leucines</term><term>Génome humain</term><term>Humains</term><term>Immunoprécipitation de la chromatine</term><term>Protéines proto-oncogènes c-myc</term><term>Régions promotrices (génétique)</term><term>Test de retard de migration électrophorétique</term><term>Éléments E-box</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>The Myc-Max heterodimer is a transcription factor that regulates expression of a large number of genes. Genome occupancy of Myc-Max is thought to be driven by Enhancer box (E-box) DNA elements, CACGTG or variants, to which the heterodimer binds <italic>in vitro</italic>.</p></sec><sec><title>Results</title><p>By analyzing ChIP-Seq datasets, we demonstrate that the positions occupied by Myc-Max across the human genome correlate with the RNA polymerase II, Pol II, transcription machinery significantly better than with E-boxes. Metagene analyses show that in promoter regions, Myc is uniformly positioned about 100 bp upstream of essentially all promoter proximal paused polymerases with Max about 15 bp upstream of Myc. We re-evaluate the DNA binding properties of full length Myc-Max proteins. Electrophoretic mobility shift assay results demonstrate Myc-Max heterodimers display significant sequence preference, but have high affinity for any DNA. Quantification of the relative affinities of Myc-Max for all possible 8-mers using universal protein-binding microarray assays shows that sequences surrounding core 6-mers significantly affect binding. Compared to the <italic>in vitro</italic> sequence preferences, Myc-Max genomic occupancy measured by ChIP-Seq is largely, although not completely, independent of sequence specificity.</p></sec><sec><title>Conclusions</title><p>We quantified the affinity of Myc-Max to all possible 8-mers and compared this with the sites of Myc binding across the human genome. Our results indicate that the genomic occupancy of Myc cannot be explained by its intrinsic DNA specificity and suggest that the transcription machinery and associated promoter accessibility play a predominant role in Myc recruitment.</p></sec><sec><title>Electronic supplementary material</title><p>The online version of this article (doi:10.1186/s13059-014-0482-3) contains supplementary material, which is available to authorized users.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Dang, Cv" uniqKey="Dang C">CV Dang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Luscher, B" uniqKey="Luscher B">B Luscher</name></author><author><name sortKey="Vervoorts, J" uniqKey="Vervoorts J">J Vervoorts</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eilers, M" uniqKey="Eilers M">M Eilers</name></author><author><name sortKey="Eisenman, Rn" uniqKey="Eisenman R">RN Eisenman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Meyer, N" uniqKey="Meyer N">N Meyer</name></author><author><name sortKey="Penn, Lz" uniqKey="Penn L">LZ Penn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lin, Cy" uniqKey="Lin C">CY Lin</name></author><author><name sortKey="Loven, J" uniqKey="Loven J">J Loven</name></author><author><name sortKey="Rahl, Pb" uniqKey="Rahl P">PB Rahl</name></author><author><name sortKey="Paranal, Rm" uniqKey="Paranal R">RM Paranal</name></author><author><name sortKey="Burge, Cb" uniqKey="Burge C">CB Burge</name></author><author><name sortKey="Bradner, Je" uniqKey="Bradner J">JE Bradner</name></author><author><name sortKey="Lee, Ti" uniqKey="Lee T">TI Lee</name></author><author><name sortKey="Young, Ra" uniqKey="Young R">RA Young</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nie, Z" uniqKey="Nie Z">Z Nie</name></author><author><name 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Burley</name></author><author><name sortKey="Roeder, Rg" uniqKey="Roeder R">RG Roeder</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Ashburner, M" uniqKey="Ashburner M">M Ashburner</name></author><author><name sortKey="Ball, Ca" uniqKey="Ball C">CA Ball</name></author><author><name sortKey="Blake, Ja" uniqKey="Blake J">JA Blake</name></author><author><name sortKey="Botstein, D" uniqKey="Botstein D">D Botstein</name></author><author><name sortKey="Butler, H" uniqKey="Butler H">H Butler</name></author><author><name sortKey="Cherry, Jm" uniqKey="Cherry J">JM Cherry</name></author><author><name sortKey="Davis, Ap" uniqKey="Davis A">AP Davis</name></author><author><name sortKey="Dolinski, K" uniqKey="Dolinski K">K Dolinski</name></author><author><name sortKey="Dwight, Ss" uniqKey="Dwight S">SS Dwight</name></author><author><name sortKey="Eppig, Jt" uniqKey="Eppig J">JT Eppig</name></author><author><name sortKey="Harris, Ma" uniqKey="Harris M">MA Harris</name></author><author><name sortKey="Hill, Dp" uniqKey="Hill D">DP Hill</name></author><author><name sortKey="Issel Tarver, L" uniqKey="Issel Tarver L">L Issel-Tarver</name></author><author><name sortKey="Kasarskis, A" uniqKey="Kasarskis A">A Kasarskis</name></author><author><name sortKey="Lewis, S" uniqKey="Lewis S">S Lewis</name></author><author><name sortKey="Matese, Jc" uniqKey="Matese J">JC Matese</name></author><author><name sortKey="Richardson, Je" uniqKey="Richardson J">JE Richardson</name></author><author><name sortKey="Ringwald, M" uniqKey="Ringwald M">M Ringwald</name></author><author><name sortKey="Rubin, Gm" uniqKey="Rubin G">GM Rubin</name></author><author><name sortKey="Sherlock, G" uniqKey="Sherlock G">G Sherlock</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Caroline du Nord</li><li>Iowa</li><li>Missouri (État)</li></region></list><tree><country name="États-Unis"><region name="Iowa"><name sortKey="Guo, Jiannan" sort="Guo, Jiannan" uniqKey="Guo J" first="Jiannan" last="Guo">Jiannan Guo</name></region><name sortKey="Cooper, Jeffrey J" sort="Cooper, Jeffrey J" uniqKey="Cooper J" first="Jeffrey J" last="Cooper">Jeffrey J. Cooper</name><name sortKey="Fordjour, Francis K" sort="Fordjour, Francis K" uniqKey="Fordjour F" first="Francis K" last="Fordjour">Francis K. Fordjour</name><name sortKey="Gordan, Raluca" sort="Gordan, Raluca" uniqKey="Gordan R" first="Raluca" last="Gordân">Raluca Gordân</name><name sortKey="Li, Tiandao" sort="Li, Tiandao" uniqKey="Li T" first="Tiandao" last="Li">Tiandao Li</name><name sortKey="Li, Tiandao" sort="Li, Tiandao" uniqKey="Li T" first="Tiandao" last="Li">Tiandao Li</name><name sortKey="Nilson, Kyle A" sort="Nilson, Kyle A" uniqKey="Nilson K" first="Kyle A" last="Nilson">Kyle A. Nilson</name><name sortKey="Price, David H" sort="Price, David H" uniqKey="Price D" first="David H" last="Price">David H. Price</name><name sortKey="Price, David H" sort="Price, David H" uniqKey="Price D" first="David H" last="Price">David H. 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