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

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.

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.

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.

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.