Research Report 2010 - MDC

esis and granulopoiesis. We showed that C/EBPα orBRM2 interact with the dimerization partner (DP) of E2Fand that BRM2 displays enhanced interaction with theE2F-DP complex. Augmented interaction with E2F-DPprevents binding of C/EBP to its cognate sites on DNAand thus prevents transactivation of C/EBP targetgenes. Repression of C/EBPα by E2F-DP occurs independentlyof pocket proteins, including the retinoblastomaprotein Rb and the related p107,and p130.Although BRM2 is more susceptible to E2F-DP repressionit retains transactivation potential and differentiationcompetence, as disclosed by knock-down of E2F orDP expression. These data suggested that a tripartidebalance between C/EBPα, E2F/DP, and pocket proteinscontrol proliferation and differentiation and that E2F-DP mediated block of C/EBPα functions may play a rolein tumorigenesis.Selected PublicationsMo X., Kowenz-Leutz E., Xu H., and Leutz A. (2004) Ras Induces MediatorComplex Exchange on C/EBPbeta. Molecular Cell, 13:241-250Mo, X., Kowenz-Leutz, E., Laumonnier, Y., Xu, H., and Leutz, A. (2005)Histone H3-tail positioning and acetylation by c-Myb but not the v-MybDNA binding SANT Domain. Genes & Development, 19: 2447-2457Scheller, M.; Huelsken, J.; Rosenbauer, F.; Taketo, M.M.; Birchmeier, W.;Tenen, G.D. and Leutz, A. (2006). Hematopoietic stem cell and multi lineagedefects by β-catenin activation. Nature Immunology, 7:1037-1047Smink, J.J, Bégay,V., Schoenmaker, T., Sterneck, E., de Vries, T.J., and Leutz, A.(2009) Transcription factor C/EBPβ isoform ratio regulates osteoclastogenesisthrough MafB. The EMBO J., 28: 1769-1781Klaus Wethmar, Valérie Bégay, Jeske J. Smink, et al. (2010) C/EBPβ ∆uORFmice−−a genetic model for uORF-mediated translational control inmammals Genes Dev. 24: 15-20Cancer Research 93