TACC3 mediates the association of MBD2 with histone acetyltransferases: a novel mechanism for reactivation of methylated promoters

Angrisano, Tiziana (2006) TACC3 mediates the association of MBD2 with histone acetyltransferases: a novel mechanism for reactivation of methylated promoters. [Tesi di dottorato] (Inedito)

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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 overexpressed. 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.

Tipologia di documento:Tesi di dottorato
Parole chiave:MBD2, TACC3, Methylation
Settori scientifico-disciplinari MIUR:Area 05 Scienze biologiche > BIO/11 BIOLOGIA MOLECOLARE
Area 06 Scienze mediche > MED/03 GENETICA MEDICA
Area 05 Scienze biologiche > BIO/13 BIOLOGIA APPLICATA
Area 06 Scienze mediche > MED/07 MICROBIOLOGIA E MICROBIOLOGIA CLINICA
Area 05 Scienze biologiche > BIO/12 BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA
Area 05 Scienze biologiche > BIO/18 GENETICA
Coordinatori della Scuola di dottorato:
Coordinatore del Corso di dottoratoe-mail (se nota)
Bruni, Carmelo Bruno
Tutor della Scuola di dottorato:
Tutor del Corso di dottoratoe-mail (se nota)
Bruni, Carmelo Bruno
Stato del full text:Accessibile
Data:2006
Numero di pagine:82
Istituzione:Università degli Studi di Napoli Federico II
Dipartimento o Struttura:Biologia e Patologia Cellulare e Molecolare "L. Califano"
Tipo di tesi:Dottorato
Stato dell'Eprint:Inedito
Denominazione del dottorato:Genetica Cellulare e Molecolare
Ciclo di dottorato:XV
Numero di sistema:895
Depositato il:28 Luglio 2008
Ultima modifica:04 Febbraio 2009 09:40

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