title: The role of acetylation in rDNA transcription.
abstract: Treatment of NIH 3T3 cells with trichostatin A (TSA), an inhibitor of histone deacetylase (HDAC), resulted in a dose-dependent increase in transcription from a rDNA reporter and from endogenous rRNA genes. Chromatin immunoprecipitation using anti-acetyl-histone H4 antibodies demonstrated a direct effect of TSA on the acetylation state of the ribosomal chromatin. TSA did not reverse inhibition of transcription from the rDNA reporter by retinoblastoma (Rb) protein, suggesting that the main mechanism by which Rb blocks rDNA transcription may not involve recruitment of deacetylases to rDNA chromatin. Overexpression of histone transacetylases p300, CBP and PCAF stimulated transcription in transfected NIH 3T3 cells. Recombinant p300, but not PCAF, stimulated rDNA transcription in vitro in the absence of nucleosomes, suggesting that the stimulation of rDNA transcription by TSA might have a chromatin-independent component. We found that the rDNA transcription factor UBF was acetylated in vivo. Finally, we also demonstrated the nucleolar localization of CBP. Our results suggest that the organization of ribosomal chromatin of higher eukaryotes is not static and that acetylation may be involved in affecting these dynamic changes directly through histone acetylation and/or through acetylation of UBF or one of the other components of rDNA transcription.
authors.affiliation: The Henry Hood Research Program, Sigfried and Janet Weis Center for Research, The Geisinger Clinic, 100 North Academy Avenue, Danville, PA 17822-2618, USA.
authors.forename: I
authors.initials: I
authors.lastname: Hirschler-Laszkiewicz
authors.forename: A
authors.initials: A
authors.lastname: Cavanaugh
authors.forename: Q
authors.initials: Q
authors.lastname: Hu
authors.forename: J
authors.initials: J
authors.lastname: Catania
authors.forename: M L
authors.initials: ML
authors.lastname: Avantaggiati
authors.forename: L I
authors.initials: LI
authors.lastname: Rothblum
mesh_terms: D016475:3T3 Cells; D000107:Acetylation; D000123:Acetyltransferases / Q000502:physiology; D000818:Animals; D050882:CREB-Binding Protein; D002466:Cell Nucleolus / Q000737:chemistry; D002843:Chromatin / Q000378:metabolism; D004275:DNA, Ribosomal / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology; D051379:Mice; D009687:Nuclear Proteins / Q000032:analysis; D035463:Pol1 Transcription Initiation Complex Proteins; D016160:Retinoblastoma Protein / Q000502:physiology; D015534:Trans-Activators / Q000032:analysis; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
chemical_list: D002843:Chromatin; D004275:DNA, Ribosomal; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D009687:Nuclear Proteins; D035463:Pol1 Transcription Initiation Complex Proteins; D016160:Retinoblastoma Protein; D015534:Trans-Activators; D014157:Transcription Factors; C063844:transcription factor UBF; C012589:trichostatin A; D000123:Acetyltransferases; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse