Differential modulation of Myb family genes by Ets-2

The myb family of genes encodes highly homologous nuclear transcription factors that play distinct roles in the development of breast, germ cells and hematoid organs. While the mechanisms associated with the regulation of these genes remain unknown, the transactivation of c-Myb was previously shown to be upregulated by transcriptional cooperation with Ets-2. The present study examines the transactivation potential of the myb gene family in cooperation with Ets-2. A-Myb and c-Myb showed similar transcriptional cooperation with Ets-2, but not with Ets-1. Interestingly, B-Myb showed no cooperative activity with Ets-2 or Ets-1. Additionally, deletion mutants of A-Myb or c-Myb, where the C-terminal negative regulatory domain was deleted, did not abrogate their ability to cooperate with Ets-2. However, the deletion mutant of B-Myb, where the C-terminal positive regulatory domain was deleted, restored its ability to cooperate with Ets-2. Furthermore, studies using a series of ‘domain-swapped’ mutants between c-Myb and B-Myb revealed that the C-terminus of B-Myb, which is responsible for the protein's transactivation potential, blocks transcriptional cooperation with Ets-2. These results suggest that the myb gene family can be differentially modulated by Ets-2, and that the C-terminus is the domain that regulates this activity.