Abstract
Previously, we demonstrated that ATF3 (activating transcription factor-3) is a stress-inducible gene, and the protein it encodes is a transcriptional repressor. In this report, 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 flanking sequence, it differs from them at the center key residues. These observations indicate that ATF3 can tolerate variations in the center of the binding sites if the flanking sequences are favorable. The repression of the ATF3 promoter by its own gene product provides a mechanistic explanation, at least in part, for the transient expression pattern of the ATF3 gene upon stress induction.
Highlights
All cells exhibit alterations in gene expression in response to extracellular stress signals such as elevated temperature, lack of nutrients, and exposure to toxins
We demonstrated that the steady-state mRNA level of ATF3 greatly increases upon exposure to a variety of stresses: seizure, toxic chemicals, mechanical injury, ischemia, and ischemia coupled with reperfusion
ATF3 Represses Transcription of Its Own Promoter—To test whether ATF3 represses the transcription of its own promoter, we cotransfected into HeLa cells a plasmid expressing ATF3 with a plasmid containing a chloramphenicol acetyltransferase (CAT) reporter driven by a 1.8-kilobase fragment of the human ATF3 promoter
Summary
All cells exhibit alterations in gene expression in response to extracellular stress signals such as elevated temperature, lack of nutrients, and exposure to toxins (for a review, see Ref. 1). 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.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
