title: Genomic binding by the Drosophila Myc, Max, Mad/Mnt transcription factor network.
abstract: 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.
authors.affiliation: Division of Basic Sciences and Divison of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
authors.forename: Amir
authors.initials: A
authors.lastname: Orian
authors.forename: Bas
authors.initials: B
authors.lastname: van Steensel
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Delrow
authors.forename: Harmen J
authors.initials: HJ
authors.lastname: Bussemaker
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Sawado
authors.forename: Eleanor
authors.initials: E
authors.lastname: Williams
authors.forename: Lenora W M
authors.initials: LW
authors.lastname: Loo
authors.forename: Shaun M
authors.initials: SM
authors.lastname: Cowley
authors.forename: Cynthia
authors.initials: C
authors.lastname: Yost
authors.forename: Sarah
authors.initials: S
authors.lastname: Pierce
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Edgar
authors.forename: Susan M
authors.initials: SM
authors.lastname: Parkhurst
authors.forename: Robert N
authors.initials: RN
authors.lastname: Eisenman
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D016153:Genes, Suppressor; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C112506:MAD protein, Drosophila; C067850:Myc associated factor X; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; D004247:DNA