MRGX is a novel transcriptional regulator that exhibits activation or repression of the B-myb promoter in a cell type-dependent manner.
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.
D001483:Base Sequence; D018797:Cell Cycle Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D018797:Cell Cycle Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C491669:MORF4L2 protein, human; C064352:MYBL2 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C012589:trichostatin A; D006655:Histone Deacetylases