Myb protein specificity: evidence of a context-specific transcription factor code

Abstract

Vertebrates express three different Myb family transcription factors, A-Myb, B-Myb, and c-Myb, that share a highly conserved DNA binding domain, bind to the same DNA sequences, and activate the same reporter gene constructs in transfection assays. However, the three Myb proteins have completely different biological roles, and microarray assays have shown that ectopic expression of each protein causes the activation of different sets of human genes. Furthermore, the genes that are activated by each protein in different cell types are distinct, suggesting that Myb transcription factors are subject to context-specific regulatory mechanisms. The data support a modification code model in which Myb proteins become decorated with different sets of posttranslational modifications in different cell types, and these modifications control the ability of the Myb proteins to interact with other cellular components that are required for activating specific sets of genes.