Interaction and functional interference of C/EBPbeta with octamer factors in immunoglobulin gene transcription.
The ubiquitous transcription factor C/EBPbeta functions as an activator or inhibitor depending on the ratios of three isoforms translated from in-frame AUG. We have identified C/EBP binding sites in both light and heavy chain immunoglobulin (Ig) promoters. Of the two C/EBP sites present in the light chain promoter, the upstream site is essential for promoter function. Mutation of this element drastically decreases promoter activity, despite the presence of an intact octamer element. Both light and heavy chain promoters were activated or inhibited by C/EBPbeta isoforms in transfected cells according to the transactivation ability of these isoforms. Endogenous IgM mRNA and protein were repressed by the inhibitory form, C/EBPbeta-3, indicating a general role of C/EBPbeta in the regulation of Ig genes. We show that C/EBPbeta-3 forms ternary complexes with Oct-1 and Oct-2 on heavy and light chain promoters, and also interacts with both octamer-binding proteins in the absence of DNA. This suggests that interference of Oct-1/Oct-2 function by C/EBPbeta-3 may account for the observed repression. Inhibition by C/EBPbeta-3 occurs not only through a C/EBP site, but also through the octamer element, as shown by co-transfection experiments with heterologous promoter constructs. Thus, C/EBPbeta regulates Ig promoter transcription by modulating octamer factor activity.
Hatada
E N
EN
Max-Delbrück-Center for Molecular Medicine Berlin, Germany.
Chen-Kiang
S
S
Scheidereit
C
C
D000818:Animals; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins / Q000502:physiology*; D005803:Genes, Immunoglobulin; D006367:HeLa Cells; D051863:Host Cell Factor C1; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000502:physiology*; D050811:Octamer Transcription Factor-1; D050813:Octamer Transcription Factor-2; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; C497692:HCFC1 protein, human; C497693:Hcfc1 protein, mouse; D051863:Host Cell Factor C1; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D009687:Nuclear Proteins; D050811:Octamer Transcription Factor-1; D050813:Octamer Transcription Factor-2; C494165:POU2F1 protein, human; C058435:POU2F2 protein, human; C494166:Pou2f1 protein, mouse; C489206:Pou2f2 protein, mouse; D014157:Transcription Factors