The chromatin remodeling factor Mi-2alpha acts as a novel co-activator for human c-Myb.

The c-Myb protein belongs to a group of early hematopoietic transcription factors that are important for progenitor generation and proliferation. These factors have been hypothesized to participate in establishing chromatin patterns specific for hematopoietic genes. In a two-hybrid screening we identified the chromatin remodeling factor Mi-2alpha as an interaction partner ...
for human c-Myb. The main interacting domains were mapped to the N-terminal region of Mi-2alpha and the DNA-binding domain of c-Myb. Surprisingly, functional analysis revealed that Mi-2alpha, previously studied as a subunit in the NuRD co-repressor complex, enhanced c-Myb-dependent reporter activation. Consistently, knock-down of endogenous Mi-2alpha in c-Myb-expressing K562 cells, led to down-regulation of the c-Myb target genes NMU and ADA. When wild-type and helicase-dead Mi-2alpha were compared, the Myb-Mi-2alpha co-activation appeared to be independent of the ATPase/DNA helicase activity of Mi-2alpha. The rationale for the unexpected co-activator function seems to lie in a dual function of Mi-2alpha, by which this factor is able to repress transcription in a helicase-dependent and activate in a helicase-independent fashion, as revealed by Gal4-tethering experiments. Interestingly, desumoylation of c-Myb potentiated the Myb-Mi-2alpha transactivational co-operation, as did co-transfection with p300.
Mesh Terms:
Adenosine Triphosphatases, Animals, COS Cells, Cells, Cultured, Cercopithecus aethiops, Chromatin Assembly and Disassembly, DNA Helicases, E1A-Associated p300 Protein, Genes, Reporter, Humans, K562 Cells, Promoter Regions, Genetic, Proto-Oncogene Proteins c-myb, SUMO-1 Protein, Trans-Activators, Transcription, Genetic, Transcriptional Activation, Transfection, Two-Hybrid System Techniques
J. Biol. Chem.
Date: May. 11, 2007
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