A simple molecular complex mediates widespread BMP-induced repression during Drosophila development.
The spatial and temporal control of gene expression during the development of multicellular organisms is regulated to a large degree by cell-cell signaling. We have uncovered a simple mechanism through which Dpp, a TGFbeta/BMP superfamily member in Drosophila, represses many key developmental genes in different tissues. A short DNA sequence, a Dpp-dependent silencer element, is sufficient to confer repression of gene transcription upon Dpp receptor activation and nuclear translocation of Mad and Medea. Transcriptional repression does not require the cooperative action of cell type-specific transcription factors but relies solely on the capacity of the silencer element to interact with Mad and Medea and to subsequently recruit the zinc finger-containing repressor protein Schnurri. Our findings demonstrate how the Dpp pathway can repress key targets in a simple and tissue-unrestricted manner in vivo and hence provide a paradigm for the inherent capacity of a signaling system to repress transcription upon pathway activation.
Pyrowolakis
George
G
Biozentrum der Universität Basel, Klingelbergstrasse 70, CH-4056, Switzerland.
Hartmann
Britta
B
Müller
Bruno
B
Basler
Konrad
K
Affolter
Markus
M
D000483:Alleles; D000818:Animals; D001665:Binding Sites; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019992:Databases as Topic; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D005982:Glutathione Transferase / Q000378:metabolism; D008954:Models, Biological; D008957:Models, Genetic; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D017354:Point Mutation; D011485:Protein Binding; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D019076:Transgenes; D016335:Zinc Fingers; D001616:beta-Galactosidase / Q000378:metabolism
D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D014157:Transcription Factors; C064196:dpp protein, Drosophila; C094066:shn protein, Drosophila; D004247:DNA; D005982:Glutathione Transferase; D001616:beta-Galactosidase