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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Gehring, Walter J. Felix, Daniel A. Fünfschilling, Raphael Cárdenas-chávez, Diana L. Papadopoulos, Dimitrios K. Canales-del-castillo, Ricardo Reséndez-pérez, Diana Villanueva-segura, Karina |
| Description | Author Affiliation: Papadopoulos DK ( Department of Cell Biology, Biozentrum, University of Basel, 4056 Basel, Switzerland.); |
| Abstract | Segmental identity along the anteroposterior axis of bilateral animals is specified by Hox genes. These genes encode transcription factors, harboring the conserved homeodomain and, generally, a YPWM motif, which binds Hox cofactors and increases Hox transcriptional specificity in vivo. Here we derive synthetic Drosophila Antennapedia genes, consisting only of the YPWM motif and homeodomain, and investigate their functional role throughout development. Synthetic peptides and full-length Antennapedia proteins cause head-to-thorax transformations in the embryo, as well as antenna-to-tarsus and eye-to-wing transformations in the adult, thus converting the entire head to a mesothorax. This conversion is achieved by repression of genes required for head and antennal development and ectopic activation of genes promoting thoracic and tarsal fates, respectively. Synthetic Antennapedia peptides bind DNA specifically and interact with Extradenticle and Bric-à-brac interacting protein 2 cofactors in vitro and ex vivo. Substitution of the YPWM motif by alanines abolishes Antennapedia homeotic function, whereas substitution of YPWM by the WRPW repressor motif, which binds the transcriptional corepressor Groucho, allows all proteins to act as repressors only. Finally, naturally occurring variations in the size of the linker between the homeodomain and YPWM motif enhance Antennapedia repressive or activating efficiency, emphasizing the importance of linker size, rather than sequence, for specificity. Our results clearly show that synthetic Antennapedia genes are functional in vivo and therefore provide powerful tools for synthetic biology. Moreover, the YPWM motif is necessary--whereas the entire N terminus of the protein is dispensable--for Antennapedia homeotic function, indicating its dual role in transcriptional activation and repression by recruiting either coactivators or corepressors. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 29 |
| Volume Number | 108 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2011-07-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Amino Acid Motifs Genetics Antennapedia Homeodomain Protein Body Patterning Drosophila Proteins Drosophila Embryology Gene Expression Regulation Animals Metabolism Basic Helix-Loop-Helix Transcription Factors Electrophoretic Mobility Shift Assay Gene Transfer Techniques Genes, Synthetic Homeodomain Proteins Immunohistochemistry Plasmids Repressor Proteins Transcription Factors Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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