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Myc-Max heterodimers activate a DEAD box gene and interact with multiple E box-related sites in vivo.

Grandori, C and Mac, J and Siëbelt, F and Ayer, D E and Eisenman, R N (1996) Myc-Max heterodimers activate a DEAD box gene and interact with multiple E box-related sites in vivo. The EMBO journal, 15 (16). pp. 4344-4357. ISSN 0261-4189

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The c-Myc protein is involved in cell proliferation, differentiation and apoptosis though heterodimerization with Max to form a transcriptionally active sequence-specific DNA binding complex. By means of sequential immunoprecipitation of chromatin using anti-Max and anti-Myc antibodies, we have identified a Myc-regulated gene and genomic sites occupied by Myc-Max in vivo. Four of 27 sites recovered by this procedure corresponded to the highest affinity 'canonical' CACGTG sequence. However, the most common in vivo binding sites belonged to the group of 'non-canonical' E box-related binding sites previously identified by in vitro selection. Several of the genomic fragments isolated contained transcribed sequences, including one, MrDb, encoding an evolutionarily conserved RNA helicase of the DEAD box family. The corresponding mRNA was induced following activation of a Myc-estrogen receptor fusion protein (Myc-ER) in the presence of a protein synthesis inhibitor, consistent with this helicase gene being a direct target of Myc-Max. In addition, as for c-Myc, the expression of MrDb is induced upon proliferative stimulation of primary human fibroblasts as well as B cells and down-regulated during terminal differentiation of HL60 leukemia cells. Our results indicate that Myc-Max heterodimers interact in vivo with a specific set of E box-related DNA sequences and that Myc is likely to activate multiple target genes including a highly conserved DEAD box protein. Therefore, Myc may exert its effects on cell behavior through proteins that affect RNA structure and metabolism.

Item Type: Article or Abstract
Additional Information: This article was originally published by Oxford University Press. No URL is available at the journal website. Full text is freely available in PubMed Central.
PubMed ID: 8861962
PMCID: PMC452159
Grant Numbers: ROCA20525
Keywords or MeSH Headings: Amino Acid Sequence; Animals; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Basic-Leucine Zipper Transcription Factors; Binding Sites; Burkitt Lymphoma/pathology; Cell Differentiation/drug effects; Cells, Cultured; Cycloheximide/pharmacology; DNA-Binding Proteins/chemistry/physiology; Dimerization; Estradiol/pharmacology; Gene Expression Regulation/drug effects; HL-60 Cells; Helix-Loop-Helix Motifs; Humans; Leucine Zippers; Molecular Sequence Data; Neoplasm Proteins/genetics/metabolism; Proto-Oncogene Proteins c-myc/chemistry/physiology; RNA Helicases; RNA Nucleotidyltransferases/genetics/metabolism; Rats; Receptors, Estrogen/genetics; Recombinant Fusion Proteins/metabolism; Regulatory Sequences, Nucleic Acid; Sequence Alignment; Sequence Homology, Amino Acid; Transcription Factors; Tumor Cells, Cultured;
Subjects: Molecules > Proteins > Transcription factors
Molecules > RNA
Molecules > Molecular structure
Molecules > Genes > Oncogenes
Cellular and Organismal Processes > Genetic processes > Transcription
Depositing User: Library Staff
Date Deposited: 26 Nov 2008 17:46
Last Modified: 21 May 2010 23:16

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