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

Kowenz-Leutz, E.; Twamley, G.; Ansieau, S.; Leutz, A.

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

Tools

PDF - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
2MB

Item Type:	Article
Title:	Novel mechanism of C/EBPbeta (NF-M) transcriptional control: activation through derepression
Creators Name:	Kowenz-Leutz, E., Twamley, G., 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
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

Repository Staff Only: item control page

Download Statistics

Downloads

Downloads per month over past year