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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.

The vertebrate A-Myb, B-Myb, and c-Myb proteins comprise a family of related transcription factors that share a highly conserved DNA binding domain. Although all three proteins are capable of binding the same sites in DNA, they have distinct, but overlapping patterns of expression and are presumed to be regulated independently. Here we show that the transcriptional activity of all three vertebrate Myb proteins can be severely inhibited by coexpression of a dominant-negative allele of p100, a coactivator protein that interacts with Myb DNA binding domains. Thus, the conserved Myb domains mediate interactions with common sites in DNA, as well as common regulators, suggesting that the proteins provide alternative or complementary responses to common upstream signaling pathways., (Copyright 2001 Academic Press.)