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

Authors :
Francesca Lembo
Tiziana Angrisano
Raffaela Pero
Vittorio Enrico Avvedimento
Carmelo B. Bruni
Francesco Di Natale
Lorenzo Chiariotti
Alfredo Fusco
Angrisano, Tiziana
Lembo, Francesca
Pero, Raffaela
Natale, F
Fusco, Alfredo
Avvedimento, VITTORIO ENRICO
Bruni, Cb
Chiariotti, Lorenzo
Source :
Europe PubMed Central, Nucleic Acids Research

Abstract

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.

Details

Database :
OpenAIRE
Journal :
Europe PubMed Central, Nucleic Acids Research
Accession number :
edsair.doi.dedup.....adedb32254b03b13806bc5e7bddc02fa