title: TACC3 mediates the association of MBD2 with histone acetyltransferases and relieves transcriptional repression of methylated promoters.
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.
authors.affiliation: Dipartimento di Biologia e Patologia Cellulare e Molecolare L. Califano, Università degli Studi di Napoli Federico II, 80131 Naples, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Angrisano
authors.forename: Francesca
authors.initials: F
authors.lastname: Lembo
authors.forename: Raffaela
authors.initials: R
authors.lastname: Pero
authors.forename: Francesco
authors.initials: F
authors.lastname: Natale
authors.forename: Alfredo
authors.initials: A
authors.lastname: Fusco
authors.forename: Vittorio E
authors.initials: VE
authors.lastname: Avvedimento
authors.forename: Carmelo B
authors.initials: CB
authors.lastname: Bruni
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Chiariotti
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology; D018385:Centrosome / Q000737:chemistry; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D020868:Gene Silencing; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D017384:Sequence Deletion; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques
chemical_list: D004268:DNA-Binding Proteins; C115368:MBD2 protein; D008869:Microtubule-Associated Proteins; C120551:TACC3 protein, human; D051548:Histone Acetyltransferases