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Nucleic Acids Research, 2000, Vol. 28, No. 2 446-453
© 2000 Oxford University Press

Myc induces the nucleolin and BN51 genes: possible implications in ribosome biogenesis

Peter J. Greasley, Claude Bonnard1 and Bruno Amati*

Cellular Growth Control Unit and 1Biocomputing Unit, Swiss Institute for Experimental Cancer Research (ISREC), 155 ch. des Boveresses, CH-1066 Epalinges, Switzerland

The c-Myc oncoprotein and its dimerization partner Max bind the DNA core consensus sequence CACGTG (E-box) and activate gene transcription. However, the low levels of induction have hindered the identification of novel Myc target genes by differential screening techniques. Here, we describe a computer-based pre-selection of candidate Myc/Max target genes, based on two restrictive criteria: an extended E-box consensus sequence for Myc/Max binding and the occurrence of this sequence within a potential genomic CpG island. Candidate genes selected by these criteria were evaluated experimentally for their response to Myc. Two Myc target genes are characterized here in detail. These encode nucleolin, an abundant nucleolar protein, and BN51, a co-factor of RNA polymerase III. Myc activates transcription of both genes via E-boxes located in their first introns, as seen for several well-characterized Myc targets. For both genes, mutation of the E-boxes abolishes transcriptional activation by Myc as well as repression by Mad1. In addition, the BN51 promoter is selectively activated by Myc and not by USF, another E-box-binding factor. Both nucleolin and BN51 are implicated in the maturation of ribosomal RNAs, albeit in different ways. We propose that Myc, via regulation of these and probably many other transcriptional targets, may be an important regulator of ribosome biogenesis.

* To whom correspondence should be addressed at present address: DNAX Research Institute, 901 California Avenue, Palo Alto, CA 94304, USA. Tel: +1 650 858 7528; Fax: +1 650 496 1200; Email: bruno.amati@dnax.org Present address: Peter J. Greasley, Institute of Pharmacology and Toxicology, University of Lausanne, 27 rue du Bugnon, CH-1005 Lausanne, Switzerland


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