MRGX Is a Novel Transcriptional Regulator That Exhibits Activation or Repression of the B-myb Promoter in a Cell Type-dependent Manner

Abstract

MRGX is a novel transcription factor that is a member of the mortality factor 4 (MORF4)-related gene family. MRG15, a closely related family member, is in a complex with the retinoblastoma tumor suppressor protein Rb and activates the B-myb promoter, which is tightly controlled by Rb/E2F through the E2F binding site. In this study we investigated the effect of MRGX on the B-myb promoter. Interestingly, MRGX repressed the B-myb promoter in EJ cells (human bladder carcinoma cells), which have a functional Rb, but activated B-myb in HeLa cells (human cervical carcinoma cells), which express a lower amount of Rb. This repression and activation was dependent on the helix-loop-helix and leucine zipper regions of the MRGX protein but not the N-terminal region. MRGX interacts with Rb through the helix-loop-helix and leucine zipper regions. Using a treatment of trichostatin A, which is a potent inhibitor of histone deacetylase (HDAC), we determined that the repression of the B-myb promoter by MRGX in EJ cells was dependent on HDAC activity. We confirmed the association of MRGX with HDAC1 by immunoprecipitation/Western analysis and determined that MRGX complexes had HDAC activity. The data indicate that MRGX can repress or activate the B-myb promoter depending on the cell type studied, suggesting that there may be tissue-specific functions of this protein.