Nucleic Acids Research, 1990, Vol. 18, No. 13 3975-3982
© 1990
MOLECULAR BIOLOGY |
CpG methylation inhibits proenkephalin gene expression and binding of the transcription factor AP-2
Department of Genetics, Harvard Medical School and Department of Molecular Biology, Massachusetts General Hospital Boston, MA, 02114, USA
*To whom correspondence should be addressed at Laboratory of Molecular Neurobiology, Neuroscience Center, Massachusetts General Hospital (East), Charlestown, MA 02129, USA.
Received January 25, 1990. Accepted April 9, 1990.
DNA methylation at Hpall (CmCGG) sites inhibits expression of a human proenkephalin-CAT fusion gene when it is transiently expressed in CV-1 cells or stably expressed in C6-glioma cells. The inhibitory effects of Hpall methylation have been mapped to a site within the human proenkephalin promoter located at position –72 relative to the start site of transcription. This region spans a cAMP and phorbol ester inducible enhancer and methylation at this position inhibits both basal transcription and transcription induced by either cAMP or TPA. The Hpall site is located within an element which binds the transcription factor AP-2. In vitro methylation at this Hpall site inhibits the binding of AP-2. These results suggest that CpG methylation inhibits proenkephalin gene expression by directly interfering with the binding of a positively acting transcription factor previously shown to be essential for maximal basal, cAMP, and TPA inducible transcription.
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