Conversion of MyoD to a neurogenic factor: binding site specificity determines lineage [ChIP-seq]. Mus musculus

MyoD and NeuroD2 are master regulators of myogenesis and neurogenesis and bind to a "shared" E-box sequence (CAGCTG) and a "private" sequence (CAGGTG or CAGATG, respectively). To determine whether private-site recognition is sufficient to confer lineage-specification, we generated a MyoD-mutant with the DNA binding specificity of NeuroD2. Our results demonstrate that redirecting MyoD binding from MyoD-private sites to NeuroD2-private sites, despite preserved binding to the MyoD/NeuroD2-shared sites, is sufficient to change MyoD from a master regulator of myogenesis to a master regulator of neurogenesis. Overall design: ChIP-seq profiling of MyoD, NeuroD2 and chimera mutants in mouse P19 cells transfected with these genes. The chimeric mutants are MyoD with the bHLH domain replaced with the NeuroD2 bHLH domain.