Differential role for CBP and p300 CREB-binding domain in motor skill learning

Cyclic adenosine monophosphate response element binding protein (CREB) binding protein (CBP) and E1A binding protein (p300) are highly homologous transcriptional coactivators with histone acetyltransferase activity. Although CBP and p300 have unique functions in vivo during embryogenesis and hematopoiesis, their functions within the nervous system remain poorly understood. The authors demonstrate that these coactivators have differential roles in motor skill learning. Mice with a mutation in the CREB-binding (KIX) domain of CBP exhibited motor learning deficits. However, mice with the analogous mutation in the KIX domain of p300 showed normal motor learning. Further, CREB knock-out mice exhibited a motor learning deficit similar to that of CBP-KIX mutant mice. These results suggest that the CREB-CBP interaction is more limiting or critical than the CREB-p300 interaction for motor skill learning. Thus, CBP and p300 are genetically distinct at the behavioral level.