Expression of the TAF4b gene is induced by MYC through a non-canonical, but not canonical, E-box which contributes to its specific response to MYC

Abstract

Transcription factor binding sites are short DNA sequences that interact with transcription factors and the proper control of gene expression appears to require the mechanisms including the regulation through the genome context around the transcription factor binding sites. The MYC proteins are central regulators of cell growth. Many genes have been reported to be regulated by MYC through E-box sites. However, the characters of E-box that Myc selects to function are not clear and identification of additional genes controlled by MYC will provide information to completely understand the functions of MYC. Here we report that MYC directly induces TAF4b expression. We mapped the transcription start site and characterized functional promoter elements for MYC response in the TAF4b promoter. There are several E-box sequences near the transcription start site, including canonical (CACGTG) and non-canonical (CGCGTG) ones. We found that c-MYC induces TAF4b expression through one of the non-canonical E-box sites, which is in a highly conserved region of TAF4b promoters in mammals, suggesting the importance of the genome context around the target E-box. When the non-canonical E-box in the TAF4b promoter was mutated to a canonical one, MYC functioned on both E-boxes, while another E-box-binding transcription factor, USF did so on only the canonical E-box. These results suggest that in addition to the context where the target E-box exists, a sequence within an E-box is involved in the mechanisms by which specific E-box sites are selected by Myc.