title: The chromatin remodeling factor Mi-2alpha acts as a novel co-activator for human c-Myb.
abstract: 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.
authors.affiliation: Department of Molecular Biosciences, University of Oslo, Oslo, Norway.
authors.forename: Thomas
authors.initials: T
authors.lastname: Saether
authors.forename: Tone
authors.initials: T
authors.lastname: Berge
authors.forename: Marit
authors.initials: M
authors.lastname: Ledsaak
authors.forename: Vilborg
authors.initials: V
authors.lastname: Matre
authors.forename: Anne Hege
authors.initials: AH
authors.lastname: Alm-Kristiansen
authors.forename: Oyvind
authors.initials: O
authors.lastname: Dahle
authors.forename: Florence
authors.initials: F
authors.lastname: Aubry
authors.forename: Odd Stokke
authors.initials: OS
authors.lastname: Gabrielsen
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D042002:Chromatin Assembly and Disassembly; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D050881:E1A-Associated p300 Protein / Q000235:genetics / Q000378:metabolism; D017930:Genes, Reporter; D006801:Humans; D020014:K562 Cells; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D011401:Promoter Regions, Genetic; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000378:metabolism; D015534:Trans-Activators; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D020798:Two-Hybrid System Techniques
chemical_list: D020598:Proto-Oncogene Proteins c-myb; D025842:SUMO-1 Protein; D015534:Trans-Activators; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D000251:Adenosine Triphosphatases; D004265:DNA Helicases; C115322:CHD3 protein, human