The Notch Pathway Intermediate HES-1 Silences CD4 Gene Expression
AUTOR(ES)
Kim, Han K.
FONTE
American Society for Microbiology
RESUMO
We have previously identified a transcriptional silencer that is critical for proper expression of the CD4 gene during T-cell development. Here we report that the Hairy/Enhancer of Split homologue HES-1, a transcription factor in the lin12/Notch signaling pathway, binds to an important functional site in the CD4 silencer. Overexpression of HES-1 leads to the silencer site-dependent repression of CD4 promoter and enhancer function as well as the downregulation of endogenous CD4 expression in CD4+ CD8− TH cells. Interestingly, overexpression of an activated form of Notch1 (NotchIC) leads to the repression of CD4 promoter and enhancer function both in the presence and absence of the silencer. NotchIC-mediated CD4 silencer function is not affected by the deletion of the HES-1-binding site, indicating that multiple factors binding to CD4 transcriptional control elements are responsive to signaling from this pathway, including other silencer-binding factors. Taken together, these data are consistent with the hypothesis that the lin12/Notch signaling pathway is important in thymic development and provide a molecular mechanism via the control of CD4 gene expression in which the lin12/Notch pathway affects T-cell developmental fate.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=109298Documentos Relacionados
- Negative Regulation of CD4 Gene Expression by a HES-1–c-Myb Complex
- Delta-1 Activation of Notch-1 Signaling Results in HES-1 Transactivation
- Dual Roles for the Notch Target Gene Hes-1 in the Differentiation of 3T3-L1 Preadipocytes
- The Notch Target Gene Hes1 Regulates Cell Cycle Inhibitor Expression in the Developing Pituitary
- Effect of CD4 gene expression on adenovirus replication.