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Nucleic Acids Research, 2000, Vol. 28, No. 10 2201-2206
© 2000 Oxford University Press

Histone deacetylase-independent transcriptional repression by methyl-CpG-binding protein 2

Fang Yu, Jens Thiesen and Wolf H. Strätling*

Institut für Medizinische Biochemie und Molekularbiologie, Universitäts-Krankenhaus Eppendorf, Martinistraße 52, D-20246 Hamburg, Germany

Methyl-CpG-binding protein 2 (MeCP2) contains a transcriptional repression domain (TRD), which can act by recruitment of a large transcriptional co-repressor complex containing histone deacetylases HDAC1 and 2. We demonstrate here that transient transcription from the SV40 enhancer/promoter or the SV40 promoter is strongly repressed in a histone deacetylase-independent manner, since repression is not alleviated by Trichostatin A (TSA). In a mutational analysis, repression depends on a conserved 30 residue sequence containing two clusters of basic amino acids. Mutation of the first of these clusters inhibits in vitro interaction between TRD and mSin3A. Furthermore, a subdomain of the TRD containing the conserved 30-residue sequence and 16 flanking amino acids was sufficient to compromise VP16-activated transcription. In summary, our results indicate an alternative, histone deacetylase-independent pathway of transcriptional repression by MeCP2.

* To whom correspondence should be addressed. Tel: +49 40 42803 2392; Fax: +49 40 42803 4862; Email: straetli@uke.uni-hamburg.de


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