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J Biol Chem, Vol. 274, Issue 16, 11399-11407, April 16, 1999
A Silencer Element in the Regulatory Region of Glutamine
Synthetase Controls Cell Type-specific Repression of Gene Induction by
Glucocorticoids
Noa
Avisar,
Liora
Shiftan,
Iris
Ben-Dror,
Nadav
Havazelet, and
Lily
Vardimon
From the Department of Biochemistry, George S. Wise Faculty of Life
Sciences, Tel Aviv University, 69978 Tel Aviv, Israel
Glutamine synthetase is a key enzyme in the
recycling of the neurotransmitter glutamate. Expression of this enzyme
is regulated by glucocorticoids, which induce a high level of glutamine
synthetase in neural but not in various non-neural tissues. This is
despite the fact that non-neural cells express functional
glucocorticoid receptor molecules capable of inducing other target
genes. Sequencing and functional analysis of the upstream region of the
glutamine synthetase gene identified, 5' to the glucocorticoid response element (GRE), a 21-base pair glutamine synthetase silencer element (GSSE), which showed considerable homology with the neural restrictive silencer element NRSE. The GSSE was able to markedly repress the induction of gene transcription by glucocorticoids in non-neural cells
and in embryonic neural retina. The repressive activity of the GSSE
could be conferred on a heterologous GRE promoter and was orientation-
and position-independent with respect to the transcriptional start
site, but appeared to depend on a location proximal to the GRE.
Gel-shift assays revealed that non-neural cells and cells of early
embryonic retina contain a high level of GSSE binding activity and that
this level declines progressively with age. Our results suggest that
the GSSE might be involved in the restriction of glutamine synthetase
induction by glucocorticoids to differentiated neural tissues.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 1999 by the American Society for Biochemistry and Molecular Biology.
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