LEF-1, a nuclear factor coordinating signaling inputs from wingless and decapentaplegic.
wingless and decapentaplegic signal during endoderm induction in Drosophila to regulate expression of the homeotic gene Ultrabithorax. Here, we define a minimal wingless response sequence in the midgut enhancer of Ultrabithorax. We show that this sequence is recognized by the murine transcription factor LEF-1 (lymphocyte enhancer binding factor 1) in a ternary complex with armadillo protein, the cytoplasmic target of the wingless signaling pathway. In stable transformants, transcriptional stimulation of the Ultrabithorax enhancer by LEF-1 depends on armadillo. Furthermore, overexpression of LEF-1 bypasses the need for wingless signaling and causes phenotypes in the midgut, notum, and wing that mimic wingless hyperstimulation. Finally, efficient transcriptional stimulation by LEF-1 in the midgut depends also on the decapentaplegic response sequence and is limited spatially by decapentaplegic signaling. Thus, LEF-1 coordinates inputs from multiple positional signals, consistent with its architectural role in regulating the assembly of multiprotein enhancer complexes.
Riese
J
J
Medical Research Council, Laboratory of Molecular Biology, Cambridge, United Kingdom.
Yu
X
X
Munnerlyn
A
A
Eresh
S
S
Hsu
S C
SC
Grosschedl
R
R
Bienz
M
M
D000818:Animals; D051186:Armadillo Domain Proteins; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins; D004742:Enhancer Elements, Genetic / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D019476:Insect Proteins / Q000378:metabolism / Q000502:physiology*; D007422:Intestines / Q000737:chemistry / Q000502:physiology; D007814:Larva / Q000737:chemistry / Q000502:physiology; D051821:Lymphoid Enhancer-Binding Factor 1; D008969:Molecular Sequence Data; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000502:physiology; D051155:Wnt1 Protein
C495305:ARM protein, Drosophila; D051186:Armadillo Domain Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D051155:Wnt1 Protein; C064196:dpp protein, Drosophila; C074622:wg protein, Drosophila