A DNA-binding-independent pathway of repression by the Drosophila Runt protein.
DNA-binding proteins are important for regulating gene expression during development. It is widely assumed that this regulation involves sequence-specific DNA binding by these transcription factors to cognate cis-regulatory sequences of their downstream target genes. However, studies in both the Drosophila and the mouse model systems have provided examples in which the DNA-binding activity of a transcription factor is not essential for in vivo function. Using a system that allows for quantitative analysis of gene function in the Drosophila embryo, we have discovered a DNA-binding-independent activity of Runt, the founding member of the RUNX family of transcriptional regulators. Examination of the in vivo potency of a DNA-binding-defective form of Runt reveals differential requirements for DNA binding in the regulation of different downstream target genes. DNA binding is not required for establishing repression of the odd-numbered stripes of the segment polarity gene engrailed, but does contribute to Runt's role as a regulator of sloppy-paired, another downstream target gene in the pathway of segmentation. We investigate this DNA-binding-independent pathway using a genetic screen for dose-dependent modifiers of runt activity. These studies reveal that DNA-binding proteins encoded by the tramtrack locus cooperate with Runt to repress engrailed. These results provide new insights into the context-dependent regulatory functions of Runt domain proteins and provide a paradigm for understanding DNA-binding-independent regulation by developmentally important transcription factors.
Vander Zwan
Christine J
CJ
Department of Biochemistry and Cell Biology and the Center for Developmental Genetics, State University of New York at Stony Brook, Stony Brook, NY 11794-5140, USA.
Wheeler
John C
JC
Li
Ling-Hui
LH
Tracey
William D
WD
Gergen
J Peter
JP
D000818:Animals; D030801:Animals, Genetically Modified; D004268:DNA-Binding Proteins / Q000235:genetics*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics*; D004625:Embryo, Nonmammalian / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D009687:Nuclear Proteins; D010641:Phenotype; D012313:RNA / Q000235:genetics; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C080833:run protein, Drosophila; D012313:RNA