The article discusses the roles of CREB-binding protein (CBP) and p300 in transcriptional regulation. Both proteins are involved in the activities of numerous transcription factors and are believed to position histone acetyltransferases (HATs) near specific nucleosomes in target gene promoter regions. They also interact with components of the general transcriptional machinery, such as TFIIID, TFIIIB, and the RNA polymerase II holoenzyme (RNAPII). The simultaneous interaction of multiple transcription factors with CBP/p300 is proposed to contribute to transcriptional synergy, while competition for their binding can mediate signal-induced transcriptional repression. The article explores whether CBP and p300 have distinct functions, reviews evidence for their regulation by phosphorylation, and discusses whether they primarily function by acetylating histones or other proteins. It also revisits the role of CBP/p300 as transcriptional "integrators" and attempts to localize their function within the complex series of processes involved in transcriptional activation. Key points include: - CBP and p300 are not completely interchangeable, with subtle differences in expression during development leading to distinct phenotypes in mice. - Phosphorylation of CBP and p300 by various kinases, including cyclin E/Cdk2, protein kinase A (PKA), calcium/calmodulin kinase IV, and pp90Rsk, regulates their function. - CBP and p300 can acetylate both histones and transcription factors, potentially providing an important mode of regulation. - CBP/p300 may function as a transcriptional integrator, mediating the activities of multiple transcription factors and being present at limiting concentrations in cells. - CBP/p300 plays a crucial role in the assembly and mobilization of the basal transcription machinery, facilitating the formation of preinitiation and reinitiation complexes, and possibly participating in termination of transcription. The article concludes by highlighting the importance of understanding the precise roles of CBP/p300 in transcriptional regulation to elucidate how cells use common transcriptional complexes to mediate specific genetic responses to diverse cellular signals.The article discusses the roles of CREB-binding protein (CBP) and p300 in transcriptional regulation. Both proteins are involved in the activities of numerous transcription factors and are believed to position histone acetyltransferases (HATs) near specific nucleosomes in target gene promoter regions. They also interact with components of the general transcriptional machinery, such as TFIIID, TFIIIB, and the RNA polymerase II holoenzyme (RNAPII). The simultaneous interaction of multiple transcription factors with CBP/p300 is proposed to contribute to transcriptional synergy, while competition for their binding can mediate signal-induced transcriptional repression. The article explores whether CBP and p300 have distinct functions, reviews evidence for their regulation by phosphorylation, and discusses whether they primarily function by acetylating histones or other proteins. It also revisits the role of CBP/p300 as transcriptional "integrators" and attempts to localize their function within the complex series of processes involved in transcriptional activation. Key points include: - CBP and p300 are not completely interchangeable, with subtle differences in expression during development leading to distinct phenotypes in mice. - Phosphorylation of CBP and p300 by various kinases, including cyclin E/Cdk2, protein kinase A (PKA), calcium/calmodulin kinase IV, and pp90Rsk, regulates their function. - CBP and p300 can acetylate both histones and transcription factors, potentially providing an important mode of regulation. - CBP/p300 may function as a transcriptional integrator, mediating the activities of multiple transcription factors and being present at limiting concentrations in cells. - CBP/p300 plays a crucial role in the assembly and mobilization of the basal transcription machinery, facilitating the formation of preinitiation and reinitiation complexes, and possibly participating in termination of transcription. The article concludes by highlighting the importance of understanding the precise roles of CBP/p300 in transcriptional regulation to elucidate how cells use common transcriptional complexes to mediate specific genetic responses to diverse cellular signals.