EID-2, a novel member of the EID family of p300-binding proteins inhibits transactivation by MyoD

Skeletal muscle differentiation has been shown to be dependent on the expression of Rb and p300. We recently cloned a novel inhibitor of muscle differentiation called EID-1, which interacted with both of these factors. In a database search for related molecules, we have cloned and characterized a new EID-1 family member, EID-2. This 28-kDa protein encodes a 236-amino-acid protein with significant similarity to EID-1 in its C-terminus. EID-2 displays developmentally regulated expression with high levels in adult heart and brain. Overexpression of EID-2 inhibits muscle-specific gene expression through inhibition of MyoD-dependent transcription. This inhibitory effect on gene expression can be explained by EID-2's ability to associate with and inhibit the acetyltransferase activity of p300. These data suggest that EID-1 and -2 represent a novel family of proteins that negatively regulate differentiation through a p300-dependent mechanism.