Related coactivators p300 and CBP affect the transcriptional activities of many transcription factors (TF), producing multiple downstream effects. Here we show that immediate early response TF, Egr1, acts upstream of p300/CBP to induce or to repress transcription, depending on the stimulus. Cells induced with serum to increase endogenous Egr1 increase the transcription of p300/CBP only when Egr1 binding sites in the promoter are not mutated, causing the expression of downstream targets of Egr1 which leads to survival and growth. Induction of p300/CBP by Egr1 results in acetylation and stabilization of Egr1 and transactivation of survival genes but repression of Egr1 and p300/CBP in negative feedback loops. In contrast, induction of Egr1 by UV-C irradiation leads to repression of p300/CBP transcription: Egr1 is preferentially phosphorylated, leading to regulation of target genes that cause cell death. This complex balance of opposing effects appears to finely modulate important cellular life and death responses.