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.
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.
Christine J
CJ
Vander Zwan
John C
JC
Wheeler
Ling-Hui
LH
Li
William D
WD
Tracey
J Peter
JP
Gergen
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