The Common Stress Responsive Transcription Factor ATF3 Binds Active Enhancers and Bookmarks Genomic Sites for Transcriptional Regulation [array]

Comprehensive analysis of global ATF3-binding profiles in the human genome under quiescent and stressed (DNA damage) conditions. Although expressed at a low level, quiescent ATF3 was found to bind a large number of genomic sites that are often associated with genes required for cellular stress responses. While these ATF3-binding sites often contained motifs for other transcription factors (TFs), we found that ATF3 bound a large portion of active enhancers characterized by p300 binding, and as a consequence, ATF3 often regulates expression of the genes proximal to these enhancers. While DNA damage elicited by camptothecin dramatically altered the ATF3 binding profile, most of the genes regulated by ATF3 upon DNA damage were pre-bound by ATF3 before the stress. Moreover, we demonstrated that ATF3 was co-localized with the major stress responder p53 at genomic sites, thereby contributing to induction of p53 target gene expression upon DNA damage. Therefore, our results suggest that ATF3 bookmarks genomic sites and interacts with other TFs for transcriptional regulation under quiescent and stressed conditions. Wild-type HCT116 (HCT116 WT) and ATF3-knockout cells (HCT116 E11) were treated with DMSO or 1.5 uM of camptothecin for 4 h. Total RNAs were prepared for microarray analyses.