Putative involvement of the histone acetyltransferase Tip60 in ribosomal gene transcription.
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.
Halkidou
Kalipso
K
Prostate Research Group, School of Surgical and Reproductive Sciences, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, UK.
Logan
Ian R
IR
Cook
Susan
S
Neal
David E
DE
Robson
Craig N
CN
D000123:Acetyltransferases / Q000032:analysis / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D002466:Cell Nucleolus / Q000737:chemistry / Q000235:genetics / Q000648:ultrastructure; D004275:DNA, Ribosomal / Q000235:genetics; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D020459:Genes, rRNA; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism; D006801:Humans; D007399:Interphase; D000074443:Lysine Acetyltransferase 5; D035463:Pol1 Transcription Initiation Complex Proteins / Q000032:analysis / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012335:RNA, Ribosomal / Q000096:biosynthesis*; D014158:Transcription, Genetic
D004275:DNA, Ribosomal; D006657:Histones; D035463:Pol1 Transcription Initiation Complex Proteins; D012335:RNA, Ribosomal; C063844:transcription factor UBF; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5; D012321:DNA-Directed RNA Polymerases