c-Myc binds to human ribosomal DNA and stimulates transcription of rRNA genes by RNA polymerase I
Autor: | Carla Grandori, Zoë A. Felton-Edkins, Celine Ngouenet, Denise A. Galloway, Natividad Gomez-Roman, Robert N. Eisenman, Robert J. White |
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Rok vydání: | 2005 |
Předmět: | |
Zdroj: | Nature Cell Biology. 7:311-318 |
ISSN: | 1476-4679 1465-7392 |
DOI: | 10.1038/ncb1224 |
Popis: | 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. |
Databáze: | OpenAIRE |
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