title: c-Myc binds to human ribosomal DNA and stimulates transcription of rRNA genes by RNA polymerase I.
abstract: c-Myc coordinates cell growth and division through a transcriptional programme that involves both RNA polymerase (Pol) II- and Pol III-transcribed genes. Here, we demonstrate that human c-Myc also directly enhances Pol I transcription of ribosomal RNA (rRNA) genes. rRNA synthesis and accumulation occurs rapidly following activation of a conditional MYC-ER allele (coding for a Myc-oestrogen-receptor fusion protein), is resistant to inhibition of Pol II transcription and is markedly reduced by c-MYC RNA interference. Furthermore, by using combined immunofluorescence and rRNA-FISH, we have detected endogenous c-Myc in nucleoli at sites of active ribosomal DNA (rDNA) transcription. Our data also show that c-Myc binds to specific consensus elements located in human rDNA and associates with the Pol I-specific factor SL1. The presence of c-Myc at specific sites on rDNA coincides with the recruitment of SL1 to the rDNA promoter and with increased histone acetylation. We propose that stimulation of rRNA synthesis by c-Myc is a key pathway driving cell growth and tumorigenesis.
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA. cgrandor@fhcrc.org
authors.forename: Carla
authors.initials: C
authors.lastname: Grandori
authors.forename: Natividad
authors.initials: N
authors.lastname: Gomez-Roman
authors.forename: Zoe A
authors.initials: ZA
authors.lastname: Felton-Edkins
authors.forename: Celine
authors.initials: C
authors.lastname: Ngouenet
authors.forename: Denise A
authors.initials: DA
authors.lastname: Galloway
authors.forename: Robert N
authors.initials: RN
authors.lastname: Eisenman
authors.forename: Robert J
authors.initials: RJ
authors.lastname: White
mesh_terms: D001665:Binding Sites; D002466:Cell Nucleolus / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D004247:DNA / Q000737:chemistry; D017931:DNA Primers / Q000737:chemistry; D004275:DNA, Ribosomal / Q000737:chemistry* / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D016193:G1 Phase; D006367:HeLa Cells; D006657:Histones / Q000737:chemistry; D006801:Humans; D047468:Immunoprecipitation; D017404:In Situ Hybridization, Fluorescence; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D009369:Neoplasms / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D034622:RNA Interference; D012318:RNA Polymerase I / Q000378:metabolism*; D012335:RNA, Ribosomal / Q000378:metabolism; D016192:Resting Phase, Cell Cycle; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers; D004275:DNA, Ribosomal; D006657:Histones; D016271:Proto-Oncogene Proteins c-myc; D012335:RNA, Ribosomal; D004247:DNA; D012318:RNA Polymerase I