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Open Access Research

Comparison of endogenous and overexpressed MyoD shows enhanced binding of physiologically bound sites

Zizhen Yao1, Abraham P Fong24, Yi Cao3, Walter L Ruzzo5, Robert C Gentleman3 and Stephen J Tapscott126*

Author Affiliations

1 Human Biology Division, Seattle, WA, USA

2 Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA, 98109, USA

3 Bioinformatics and Computational Biology, Genentech, South San Francisco, CA, USA

4 Department of Pediatrics, University of Washington, School of Medicine, Seattle, WA, 98105, USA

5 Departments of Computer Science and Engineering and Genome Sciences, Seattle, WA, USA

6 Department of Neurology, University of Washington, School of Medicine, Seattle, WA, 98105, USA

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Skeletal Muscle 2013, 3:8  doi:10.1186/2044-5040-3-8

Published: 8 April 2013

Abstract

Background

Transcription factor overexpression is common in biological experiments and transcription factor amplification is associated with many cancers, yet few studies have directly compared the DNA-binding profiles of endogenous versus overexpressed transcription factors.

Methods

We analyzed MyoD ChIP-seq data from C2C12 mouse myotubes, primary mouse myotubes, and mouse fibroblasts differentiated into muscle cells by overexpression of MyoD and compared the genome-wide binding profiles and binding site characteristics of endogenous and overexpressed MyoD.

Results

Overexpressed MyoD bound to the same sites occupied by endogenous MyoD and possessed the same E-box sequence preference and co-factor site enrichments, and did not bind to new sites with distinct characteristics.

Conclusions

Our data demonstrate a robust fidelity of transcription factor binding sites over a range of expression levels and that increased amounts of transcription factor increase the binding at physiologically bound sites.

Keywords:
Transcription factor; Overexpressed; MyoD; c-Myc; ChIP-seq