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J. Biol. Chem., Vol. 276, Issue 17, 13917-13923, April 27, 2001
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From the The repressor element-1/neuron-restrictive
silencing element (RE-1/NRSE) mediates transcriptional repression by
the repressor element silencing transcription factor/neuron-restrictive
silencing factor (REST/NRSF) in many neuron-specific genes. REST/NRSF
is expressed most highly in non-neural tissues, where it is thought to
repress gene transcription, but is also found in developing neurons and
at low levels in the brain. Its null mutation in vivo results in embryonic lethality in mice. While the RE-1/NRSE-mediated repressive influence of REST/NRSF is well established, results in
transgenic studies have suggested that the action of the system is more
complex. Here, we report that transcription of the corticotropin releasing hormone (CRH) gene is regulated by REST/NRSF, in part through
the RE-1/NRSE. Expression of transfected Crh-luciferase constructs was down-regulated by REST/NRSF in a
RE-1/NRSE-dependent fashion in both muscle-derived L6 and
REST/NRSF co-transfected neuronal PC12 cells. Treatment of L6 cells
with trichostatin A revealed that REST/NRSF repression depends,
in part, on histone deacetylase activity in these cells. In another
neuronal cell line, NG108, REST/NRSF also repressed expression from
constructs containing an intact RE-1/NRSE. However, unexpectedly,
REST/NRSF up-regulated expression levels of constructs lacking an
intact RE-1/NRSE. These results suggest that REST/NRSF can act as both a repressor of Crh transcription, via the Crh
RE-1/NRSE, and an enhancer of Crh transcription, via a
mechanism independent of the Crh RE-1/NRSE.
Repressor Element Silencing Transcription
Factor/Neuron-restrictive Silencing Factor (REST/NRSF) Can Act
as an Enhancer as Well as a Repressor of Corticotropin-releasing
Hormone Gene Transcription*
§ and Program in Neuroscience, Harvard Medical
School, and the § Division of Endocrinology, Children's
Hospital, Harvard Medical School,
Boston, Massachusetts 02115
*
This work was supported in part by grants from the National
Institutes of Health (to J. M. and K. S.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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