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Molecular and Cellular Biology, December 1998, p. 7166-7175, Vol. 18, No. 12
Department of Microbiology, Columbia
University College of Physicians and Surgeons, New York, New York 10032
Received 24 April 1998/Returned for modification 15 May
1998/Accepted 10 September 1998
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
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Copyright © 1998, American Society for Microbiology. All rights reserved.
The Notch Pathway Intermediate HES-1 Silences
CD4 Gene Expression
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.
*
Corresponding author. Mailing address: Department of
Microbiology, Columbia University College of Physicians and Surgeons, 701 West 168th St., New York, NY 10032. Phone: (212) 305-2743. Fax:
(212) 305-8013. E-mail:
siu{at}cusiu3.cpmc.columbia.edu.
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