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Published online 11 March 2004

Nucleic Acids Research, 2004, Vol. 32, No. 5 1654-1665
© 2004 Oxford University Press

Putative involvement of the histone acetyltransferase Tip60 in ribosomal gene transcription

Kalipso Halkidou, Ian R. Logan, Susan Cook, David E. Neal1 and Craig N. Robson*

Prostate Research Group, School of Surgical and Reproductive Sciences, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, UK and 1 Oncology Centre, Addenbrooke’s Hospital, Cambridge CB2 2QQ, UK

*To whom correspondence should be addressed. Tel: +44 191 2227076; Fax: +44 191 2228514; Email: c.n.robson{at}ncl.ac.uk

Tip60 is a histone acetyltransferase (HAT) implicated in a wide range of cellular functions, including mRNA synthesis and DNA repair. In the present report we propose a model based on which Tip60 is actively involved in ribosomal gene transcription through acetylation of UBF, a ribosomal specific transcription factor, as well as through its direct recruitment to the human ribosomal gene promoter, as shown by chromatin immunoprecipitation experiments. Electron microscopy studies revealed that Tip60 resides in sites of active rDNA transcription within the nucleolus, while it co-localizes with UBF as shown by confocal microscopy. In addition, in vivo transcription assays demonstrated that the nucleolar fraction of Tip60 localizes to sites of newly synthesized rRNA. Finally, functional assays established that Tip60 complexes with, and targets UBF for acetylation. The present study underlines the importance of acetylation in rDNA transcription and directly implicates Tip60 in the process of ribosomal gene transcription.


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