TACC3 mediates the association of MBD2 with histone acetyltransferases and relieves transcriptional repression of methylated promoters.

Dipartimento di Biologia e Patologia Cellulare e Molecolare L. Califano, Universita degli Studi di Napoli Federico II, 80131 Naples, Italy.
We have recently reported that a novel MBD2 interactor (MBDin) has the capacity to reactivate transcription from MBD2-repressed methylated promoters even in the absence of demethylation events. Here we show that another unrelated protein, TACC3, displays a similar activity on methylated genes. In addition the data reported here provide possible molecular mechanisms for the observed phenomenon. Immunoprecipitation experiments showed that MBD2/TACC3 form a complex in vivo with the histone acetyltransferase pCAF. MBD2 could also associate with HDAC2, a component of MeCP1 repression complex. However, we found that the complexes formed by MBD2 with TACC3/pCAF and with HDAC2 were mutually exclusive. Moreover, HAT enzymatic assays demonstrated that HAT activity associates with MBD2 in vivo and that such association significantly increased when TACC3 was over-expressed. Overall our findings suggest that TACC3 can be recruited by MBD2 on methylated promoters and is able to reactivate transcription possibly by favoring the formation of an HAT-containing MBD2 complex and, thus, switching the repression potential of MBD2 in activation even prior to eventual demethylation.
Mesh Terms:
Animals, Cell Nucleus, Centrosome, DNA Methylation, DNA-Binding Proteins, Gene Silencing, Histone Acetyltransferases, Humans, Immunoprecipitation, Microtubule-Associated Proteins, Promoter Regions, Genetic, Sequence Deletion, Transcription, Genetic, Transcriptional Activation, Two-Hybrid System Techniques
Nucleic Acids Res. Jan. 18, 2006; 34(1);364-72 [PUBMED:16410616]
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