Abstract
Abstract A43: Sequence specificity incompletely defines the genome-wide occupancy of Myc
Molecular cancer research, Vol.13(10_Supplement), pp.A43-A43
10/01/2015
DOI: 10.1158/1557-3125.MYC15-A43
Abstract
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 in the context of accessible chromatin. Results: By analyzing ChIP-Seq datasets, we demonstrated that the positions occupied by Myc-Max across the human genome correlate with the RNA polymerase II (Pol II) transcription machinery better than with E-boxes. Metagene analyses showed that in promoter regions, Myc was uniformly positioned about 100 bp upstream of essentially all promoter proximal paused polymerases with Max about 15 bp upstream of Myc. We re-evaluated the DNA binding properties of full length Myc-Max proteins using electrophoretic mobility shift assays (EMSA) and universal protein-binding microarrays (PBM). EMSA results demonstrated 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 PBM assays showed that sequences surrounding core 6-mers significantly affect binding. Compared to the in vitro sequence preferences, Myc-Max genomic occupancy measured by ChIP-Seq was largely, although not completely, independent of sequence specificity. Conclusions: Our results indicate that the genomic occupancy of Myc cannot be explained solely by its intrinsic DNA specificity and suggest that the transcription machinery and associated promoter accessibility play a predominant role in Myc recruitment. Citation Format: Jiannan Guo, Tiandao Li, Joshua Schipper, Kyle A. Nilson, Francis K. Fordjour, Jeffrey J. Cooper, Raluca Gordan, David H. Price. Sequence specificity incompletely defines the genome-wide occupancy of Myc. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr A43.
Details
- Title: Subtitle
- Abstract A43: Sequence specificity incompletely defines the genome-wide occupancy of Myc
- Creators
- Jiannan Guo - University of PennsylvaniaTiandao Li - Washington University in St. LouisJoshua Schipper - Duke UniversityKyle A. Nilson - University of IowaFrancis K. Fordjour - Johns Hopkins UniversityJeffrey J. Cooper - University of IowaRaluca Gordan - Duke UniversityDavid H. Price - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Molecular cancer research, Vol.13(10_Supplement), pp.A43-A43
- DOI
- 10.1158/1557-3125.MYC15-A43
- ISSN
- 1541-7786
- eISSN
- 1557-3125
- Language
- English
- Date published
- 10/01/2015
- Academic Unit
- Surgery; Biochemistry and Molecular Biology
- Record Identifier
- 9984297459602771
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