title: UBF levels determine the number of active ribosomal RNA genes in mammals.
abstract: In mammals, the mechanisms regulating the number of active copies of the approximately 200 ribosomal RNA (rRNA) genes transcribed by RNA polymerase I are unclear. We demonstrate that depletion of the transcription factor upstream binding factor (UBF) leads to the stable and reversible methylation-independent silencing of rRNA genes by promoting histone H1-induced assembly of transcriptionally inactive chromatin. Chromatin remodeling is abrogated by the mutation of an extracellular signal-regulated kinase site within the high mobility group box 1 domain of UBF1, which is required for its ability to bend and loop DNA in vitro. Surprisingly, rRNA gene silencing does not reduce net rRNA synthesis as transcription from remaining active genes is increased. We also show that the active rRNA gene pool is not static but decreases during differentiation, correlating with diminished UBF expression. Thus, UBF1 levels regulate active rRNA gene chromatin during growth and differentiation.
authors.affiliation: Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia.
authors.forename: Elaine
authors.initials: E
authors.lastname: Sanij
authors.forename: Gretchen
authors.initials: G
authors.lastname: Poortinga
authors.forename: Kerith
authors.initials: K
authors.lastname: Sharkey
authors.forename: Sandy
authors.initials: S
authors.lastname: Hung
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Holloway
authors.forename: Jaclyn
authors.initials: J
authors.lastname: Quin
authors.forename: Elysia
authors.initials: E
authors.lastname: Robb
authors.forename: Lee H
authors.initials: LH
authors.lastname: Wong
authors.forename: Walter G
authors.initials: WG
authors.lastname: Thomas
authors.forename: Victor
authors.initials: V
authors.lastname: Stefanovsky
authors.forename: Tom
authors.initials: T
authors.lastname: Moss
authors.forename: Lawrence
authors.initials: L
authors.lastname: Rothblum
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Hannan
authors.forename: Grant A
authors.initials: GA
authors.lastname: McArthur
authors.forename: Richard B
authors.initials: RB
authors.lastname: Pearson
authors.forename: Ross D
authors.initials: RD
authors.lastname: Hannan
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D019175:DNA Methylation; D004275:DNA, Ribosomal / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D020868:Gene Silencing; D020459:Genes, rRNA / Q000235:genetics*; D024742:HMG-Box Domains; D006657:Histones / Q000378:metabolism; D051379:Mice; D008957:Models, Genetic; D041681:NIH 3T3 Cells; D035463:Pol1 Transcription Initiation Complex Proteins / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D012318:RNA Polymerase I / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D004275:DNA, Ribosomal; D006657:Histones; D035463:Pol1 Transcription Initiation Complex Proteins; D020033:Protein Isoforms; C063844:transcription factor UBF; D012318:RNA Polymerase I