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Novel mechanism of C/EBPbeta (NF-M) transcriptional control: activation through derepression

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Item Type:Article
Title:Novel mechanism of C/EBPbeta (NF-M) transcriptional control: activation through derepression
Creators Name:Kowenz-Leutz, E. and Twamley, G. and Ansieau, S. and Leutz, A.
Abstract:Phosphorylation of transcription factors is regarded as a major mechanism to control their activity in regulation of gene expression. C/EBP beta is a transcription factor that becomes activated after phosphorylation to induce genes involved in inflammation, acute-phase response, cytokine expression, cell growth, and differentiation. The chicken homolog NF-M collaborates with Myb and various kinase oncogenes in normal myeloid differentiation as well as in the leukemic transformation of myelomonocytic cells. Here, we examined the structure of NF-M and its mechanism of activation. We show that NF-M is a repressed transcription factor with concealed activation potential. Derepressed NF-M exhibits enhanced transcriptional efficacy in reporter assays. More importantly, NF-M activates resident chromatin-embedded, myelomonocyte-specific target genes, even in heterologous cell types such as fibroblasts or erythroblasts. We identified two regions within NF-M that act to repress trans-activation. Repression is abolished by deletion of these regions, activation of signal transduction kinases including v-erbB, polyoma middle T, ras and mil/raf, or point mutation of a critical phosphorylation site for MAP kinases. We provide evidence that phosphorylation plays a unique role to derepress rather than to enhance the trans-activation domain as a novel mechanism to regulate gene expression by NF-M/C/EBP beta.
Keywords:C/EBPbeta, Oncogenes, Transcription, Phosphorylation, Gene Activation, Animals, Chickens
Source:Genes & Development
ISSN:0890-9369
Publisher:Cold Spring Harbor Laboratory Press (U.S.A.)
Volume:8
Number:22
Page Range:2781-2791
Date:15 November 1994
Official Publication:https://doi.org/10.1101/gad.8.22.2781
PubMed:View item in PubMed

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