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
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