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Sequence specificity incompletely defines the genome-wide occupancy of Myc.

Publication ,  Journal Article
Guo, J; Li, T; Schipper, J; Nilson, KA; Fordjour, FK; Cooper, JJ; Gordân, R; Price, DH
Published in: Genome Biol
2014

BACKGROUND: 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 in vitro. RESULTS: 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 in vitro sequence preferences,Myc-Max genomic occupancy measured by ChIP-Seq is largely, although not completely, independent of sequence specificity. CONCLUSIONS: 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.

Duke Scholars

Published In

Genome Biol

DOI

EISSN

1474-760X

Publication Date

2014

Volume

15

Issue

10

Start / End Page

482

Location

England

Related Subject Headings

  • Transcription, Genetic
  • Sequence Analysis, DNA
  • RNA Polymerase II
  • Proto-Oncogene Proteins c-myc
  • Promoter Regions, Genetic
  • Humans
  • Genome, Human
  • Electrophoretic Mobility Shift Assay
  • E-Box Elements
  • Chromatin Immunoprecipitation
 

Citation

APA
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MLA
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Guo, J., Li, T., Schipper, J., Nilson, K. A., Fordjour, F. K., Cooper, J. J., … Price, D. H. (2014). Sequence specificity incompletely defines the genome-wide occupancy of Myc. Genome Biol, 15(10), 482. https://doi.org/10.1186/s13059-014-0482-3
Guo, Jiannan, Tiandao Li, Joshua Schipper, Kyle A. Nilson, Francis K. Fordjour, Jeffrey J. Cooper, Raluca Gordân, and David H. Price. “Sequence specificity incompletely defines the genome-wide occupancy of Myc.Genome Biol 15, no. 10 (2014): 482. https://doi.org/10.1186/s13059-014-0482-3.
Guo J, Li T, Schipper J, Nilson KA, Fordjour FK, Cooper JJ, et al. Sequence specificity incompletely defines the genome-wide occupancy of Myc. Genome Biol. 2014;15(10):482.
Guo, Jiannan, et al. “Sequence specificity incompletely defines the genome-wide occupancy of Myc.Genome Biol, vol. 15, no. 10, 2014, p. 482. Pubmed, doi:10.1186/s13059-014-0482-3.
Guo J, Li T, Schipper J, Nilson KA, Fordjour FK, Cooper JJ, Gordân R, Price DH. Sequence specificity incompletely defines the genome-wide occupancy of Myc. Genome Biol. 2014;15(10):482.

Published In

Genome Biol

DOI

EISSN

1474-760X

Publication Date

2014

Volume

15

Issue

10

Start / End Page

482

Location

England

Related Subject Headings

  • Transcription, Genetic
  • Sequence Analysis, DNA
  • RNA Polymerase II
  • Proto-Oncogene Proteins c-myc
  • Promoter Regions, Genetic
  • Humans
  • Genome, Human
  • Electrophoretic Mobility Shift Assay
  • E-Box Elements
  • Chromatin Immunoprecipitation