THE TRANSCRIPTIONAL INTEGRATOR CREB-BINDING PROTEIN MEDIATES POSITIVECROSS-TALK BETWEEN NUCLEAR HORMONE RECEPTORS AND THE HEMATOPOIETIC BZIP PROTEIN P45 NF-E2/

Thyroid hormone (T3) and retinoic acid (RA) play important roles in er ythropoiesis. We found that the hematopoietic cell-specific bZip prote in p45/NF-E2 interacts with T3 receptor (TR) and RA receptor (RAR) but not retinoid X receptor. The interaction is between the DNA-binding d omain of the nuclear receptor and the leucine zipper region of p45/NF- E2 but is markedly enhanced by cognate ligand. Remarkably, ligand-depe ndent transactivation by TR and RAR is markedly potentiated by p45/NF- E2. This effect of p45/NF-E2 is prevented by maf-like protein p18, whi ch functions positively as a heterodimer with p45/NF-E2 on DNA. Potent iation of hormone action by p45/NF-E2 requires its activation domain, which interacts strongly with the multifaceted coactivator cyclic AMP response element protein-binding protein (CBP). The region of CBP whic h interacts with p45/NF-E2 is the same interaction domain that mediate s inhibition of hormone-stimulated transcription by AP1 transcription factors. Overexpression of the bZip interaction domain of CBP specific ally abolishes the positive cross talk between TR and p45/NF-E2. Thus, positive cross talk between p15/NF-E2 and nuclear hormone receptors r equires direct protein-protein interactions between these factors and, vith CBP, whose integration of positive signals from two transactivati on domains provides a novel mechanism for potentiation of hormone acti on in hematopoietic cells.