Transcriptional autorepression of the stress-inducible gene ATF3

Previously, we demonstrated that ATF3 ((a) under bar ctivating (t) under ba r ranscription (f) under bar actor-(3) under bar) is a stress-inducible gen e, and the protein it encodes is a transcriptional repressor. In this repor t, we present evidence suggesting that ATF3 represses the transcription of its own gene. Interestingly, efficient repression requires a consensus ATF/ cAMP-responsive element site in the promoter and a previously unidentified ATF3-binding site immediately downstream from the TATA box. Although this new site resembles the known ATF/cAMP-responsive element sequences at the f lanking sequence, it differs from them at the center key residues. These ob servations indicate that ATF3 can tolerate variations in the center of the binding sites if the flanking sequences are favorable. The repression of th e ATF3 promoter by its own gene product provides a mechanistic explanation, at least in part, for the transient expression pattern of the ATF3 gene up on stress induction.