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Genomic binding by the Drosophila Myc, Max, Mad/Mnt transcription factor network.

Orian, Amir and van Steensel, Bas and Delrow, Jeffrey and Bussemaker, Harmen J and Li, Ling and Sawado, Tomoyuki and Williams, Eleanor and Loo, Lenora W M and Cowley, Shaun M and Yost, Cynthia and Pierce, Sarah and Edgar, Bruce A and Parkhurst, Susan M and Eisenman, Robert N (2003) Genomic binding by the Drosophila Myc, Max, Mad/Mnt transcription factor network. Genes & development, 17 (9). pp. 1101-1114. ISSN 0890-9369

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The Myc/Max/Mad transcription factor network is critically involved in cell behavior; however, there is relatively little information on its genomic binding sites. We have employed the DamID method to carry out global genomic mapping of the Drosophila Myc, Max, and Mad/Mnt proteins. Each protein was tethered to Escherichia coli DNA adenine-methyltransferase (Dam) permitting methylation proximal to in vivo binding sites in Kc cells. Microarray analyses of methylated DNA fragments reveals binding to multiple loci on all major Drosophila chromosomes. This approach also reveals dynamic interactions among network members as we find that increased levels of dMax influence the extent of dMyc, but not dMnt, binding. Computer analysis using the REDUCE algorithm demonstrates that binding regions correlate with the presence of E-boxes, CG repeats, and other sequence motifs. The surprisingly large number of directly bound loci ( approximately 15% of coding regions) suggests that the network interacts widely with the genome. Furthermore, we employ microarray expression analysis to demonstrate that hundreds of DamID-binding loci correspond to genes whose expression is directly regulated by dMyc in larvae. These results suggest that a fundamental aspect of Max network function involves widespread binding and regulation of gene expression.

Item Type: Article or Abstract
Additional Information: This article is freely available in PubMed Central and at the journal's website.
DOI: 10.1101/gad.1066903
PubMed ID: 12695332
PMCID: PMC196053
Grant Numbers: GM47852, CA80295-03S, 1P20LM007276-01, RO1CA57138, P30 CA15704-29, R01 GM51186
Keywords or MeSH Headings: Animals; Basic-Leucine Zipper Transcription Factors; DNA/metabolism; DNA-Binding Proteins/genetics/metabolism; Drosophila/genetics/metabolism; Drosophila Proteins/genetics/metabolism; Genes, Suppressor; Nuclear Proteins/genetics/metabolism; Proto-Oncogene Proteins c-myc/genetics/metabolism; Transcription Factors/genetics/metabolism;
Subjects: Molecules > Proteins > Transcription factors
Molecules > Molecular structure
Molecules > Genes > Oncogenes
Research Methodologies > Genomics > Gene mapping
Depositing User: Library Staff
Date Deposited: 24 Nov 2008 19:47
Last Modified: 07 May 2010 21:50

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