Grandori, Carla and Gomez-Roman, Natividad and Felton-Edkins, Zoe A and Ngouenet, Celine and Galloway, Denise A and Eisenman, Robert N and White, Robert J (2005) c-Myc binds to human ribosomal DNA and stimulates transcription of rRNA genes by RNA polymerase I. Nature cell biology, 7 (3). pp. 311-318. ISSN 1465-7392Full text not available from this repository.
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.
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|Keywords or MeSH Headings:||Binding Sites; Cell Nucleolus/metabolism; Cell Nucleus/metabolism; Cell Proliferation; Chromatin Immunoprecipitation; DNA/chemistry; DNA Primers/chemistry; DNA, Ribosomal/chemistry/metabolism; Fibroblasts/metabolism; G0 Phase; G1 Phase; Hela Cells; Histones/chemistry; Humans; Immunoprecipitation; In Situ Hybridization, Fluorescence; Microscopy, Fluorescence; Models, Genetic; Neoplasms/metabolism; Promoter Regions (Genetics); Protein Binding; Proto-Oncogene Proteins c-myc/metabolism; RNA Interference; RNA Polymerase I/metabolism; RNA, Ribosomal/metabolism; Retroviridae/genetics; Reverse Transcriptase Polymerase Chain Reaction; Time Factors; Transcription, Genetic;|
|Subjects:||Molecules > RNA
Cellular and Organismal Processes > Cell Physiology > Cell proliferation
Molecules > Genes > Oncogenes
Cellular and Organismal Processes > Genetic processes > Transcription
|Depositing User:||Library Staff|
|Date Deposited:||12 Dec 2008 23:37|
|Last Modified:||11 Oct 2011 00:35|
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