Sequence specificity incompletely defines the genome-wide occupancy of Myc

Jiannan Guo; Tiandao Li; Joshua Schipper; Kyle A Nilson; Francis K Fordjour; Jeffrey J Cooper; Raluca Gordân; David H Price

doi:10.1186/s13059-014-0482-3

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Sequence specificity incompletely defines the genome-wide occupancy of Myc

Journal article

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Sequence specificity incompletely defines the genome-wide occupancy of Myc

Jiannan Guo, Tiandao Li, Joshua Schipper, Kyle A Nilson, Francis K Fordjour, Jeffrey J Cooper, Raluca Gordân and David H Price

GenomeBiology.com, Vol.15(10), pp.482-482

2014

DOI: 10.1186/s13059-014-0482-3

PMCID: PMC4242493

PMID: 25287278

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Abstract

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.

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Title: Subtitle: Sequence specificity incompletely defines the genome-wide occupancy of Myc
Creators: Jiannan Guo - Department of Biochemistry, University of Iowa, Iowa City, IA 52242 USA
Tiandao Li - Department of Biochemistry, University of Iowa, Iowa City, IA 52242 USA
Joshua Schipper - Institute for Genome Sciences and Policy, Duke University, Durham, NC 27708 USA
Kyle A Nilson - Molecular and Cellular Biology Program, University of Iowa, Iowa City, IA 52242 USA
Francis K Fordjour - Department of Biochemistry, University of Iowa, Iowa City, IA 52242 USA
Jeffrey J Cooper - Department of Biochemistry, University of Iowa, Iowa City, IA 52242 USA
Raluca Gordân - Institute for Genome Sciences and Policy, Duke University, Durham, NC 27708 USA
David H Price - Department of Biochemistry, University of Iowa, Iowa City, IA 52242 USA
Resource Type: Journal article
Publication Details: GenomeBiology.com, Vol.15(10), pp.482-482
DOI: 10.1186/s13059-014-0482-3
PMID: 25287278
PMCID: PMC4242493
NLM abbreviation: Genome Biol
ISSN: 1465-6906
eISSN: 1465-6914
Publisher: BioMed Central; London
Language: English
Date published: 2014
Academic Unit: Surgery; Biochemistry and Molecular Biology
Record Identifier: 9984024532402771

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