Developmentally regulated expression of the transcriptional cofactors/histone acetyltransferases CBP and p300 during...

CBP (CREBBP/CREB-binding protein) and p300 are related signal-dependent transcriptional cofactors and histone acetyltransferases. They are both implicated in tumorigenesis and mutations in the human CBP gene have been found in Rubinstein-Taybi syndrome (RTS), which is characterized by multiple developmental defects and mental retardation. Studies with CBP and p300 mouse mutants indicate that both proteins are required for normal development, and that there is an essential gene dosage-sensitive role for these transcriptional cofactors in embryogenesis, cell differentiation and proliferation. Although it is generally believed that the expression of CBP and p300 is ubiquitous, we report here that they are developmentally regulated during mouse embryogenesis. In the developing CNS, CBP and p300 proteins were found throughout the newly formed neural plate, but their expression was later restricted to the dorsal parts of the developing neural tube. Later in neural development, CBP and p300 proteins could also be found in subsets of ventral neurons, including motor neurons and oligodendrocytes. During organogenesis, CBP and p300 proteins were expressed in specific cell types of the developing heart, vasculature, skin, lung and liver. Many of these tissues and organs are known to be affected in mutant mice lacking CBP and/or p300, and in RTS patients. Interestingly, while CBP and p300 proteins show extensive overlapping expression during mouse embryogenesis, we observed that their subcellular localization is developmentally regulated in several cell types. Taken together, our results suggest that there are common, as well as distinct, biochemical functions of CBP and p300 during mouse development.