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Distinct Contributions of Conserved Modules to Runt Transcription Factor Activity

Runx proteins play vital roles in regulating transcription in numerous developmental pathways throughout the animal kingdom. Two Runx protein hallmarks are the DNA-binding Runt domain and a C-terminal VWRPY motif that mediates interaction with TLE/Gro corepressor proteins. A phylogenetic analysis of...

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Autores principales: Walrad, Pegine B., Hang, Saiyu, Joseph, Genevieve S., Salas, Julia, Gergen, J. Peter
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893994/
https://www.ncbi.nlm.nih.gov/pubmed/20462957
http://dx.doi.org/10.1091/mbc.E09-11-0953
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author Walrad, Pegine B.
Hang, Saiyu
Joseph, Genevieve S.
Salas, Julia
Gergen, J. Peter
author_facet Walrad, Pegine B.
Hang, Saiyu
Joseph, Genevieve S.
Salas, Julia
Gergen, J. Peter
author_sort Walrad, Pegine B.
collection PubMed
description Runx proteins play vital roles in regulating transcription in numerous developmental pathways throughout the animal kingdom. Two Runx protein hallmarks are the DNA-binding Runt domain and a C-terminal VWRPY motif that mediates interaction with TLE/Gro corepressor proteins. A phylogenetic analysis of Runt, the founding Runx family member, identifies four distinct regions C-terminal to the Runt domain that are conserved in Drosophila and other insects. We used a series of previously described ectopic expression assays to investigate the functions of these different conserved regions in regulating gene expression during embryogenesis and in controlling axonal projections in the developing eye. The results indicate each conserved region is required for a different subset of activities and identify distinct regions that participate in the transcriptional activation and repression of the segmentation gene sloppy-paired-1 (slp1). Interestingly, the C-terminal VWRPY-containing region is not required for repression but instead plays a role in slp1 activation. Genetic experiments indicating that Groucho (Gro) does not participate in slp1 regulation further suggest that Runt's conserved C-terminus interacts with other factors to promote transcriptional activation. These results provide a foundation for further studies on the molecular interactions that contribute to the context-dependent properties of Runx proteins as developmental regulators.
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spelling pubmed-28939942010-09-16 Distinct Contributions of Conserved Modules to Runt Transcription Factor Activity Walrad, Pegine B. Hang, Saiyu Joseph, Genevieve S. Salas, Julia Gergen, J. Peter Mol Biol Cell Articles Runx proteins play vital roles in regulating transcription in numerous developmental pathways throughout the animal kingdom. Two Runx protein hallmarks are the DNA-binding Runt domain and a C-terminal VWRPY motif that mediates interaction with TLE/Gro corepressor proteins. A phylogenetic analysis of Runt, the founding Runx family member, identifies four distinct regions C-terminal to the Runt domain that are conserved in Drosophila and other insects. We used a series of previously described ectopic expression assays to investigate the functions of these different conserved regions in regulating gene expression during embryogenesis and in controlling axonal projections in the developing eye. The results indicate each conserved region is required for a different subset of activities and identify distinct regions that participate in the transcriptional activation and repression of the segmentation gene sloppy-paired-1 (slp1). Interestingly, the C-terminal VWRPY-containing region is not required for repression but instead plays a role in slp1 activation. Genetic experiments indicating that Groucho (Gro) does not participate in slp1 regulation further suggest that Runt's conserved C-terminus interacts with other factors to promote transcriptional activation. These results provide a foundation for further studies on the molecular interactions that contribute to the context-dependent properties of Runx proteins as developmental regulators. The American Society for Cell Biology 2010-07-01 /pmc/articles/PMC2893994/ /pubmed/20462957 http://dx.doi.org/10.1091/mbc.E09-11-0953 Text en © 2010 by The American Society for Cell Biology
spellingShingle Articles
Walrad, Pegine B.
Hang, Saiyu
Joseph, Genevieve S.
Salas, Julia
Gergen, J. Peter
Distinct Contributions of Conserved Modules to Runt Transcription Factor Activity
title Distinct Contributions of Conserved Modules to Runt Transcription Factor Activity
title_full Distinct Contributions of Conserved Modules to Runt Transcription Factor Activity
title_fullStr Distinct Contributions of Conserved Modules to Runt Transcription Factor Activity
title_full_unstemmed Distinct Contributions of Conserved Modules to Runt Transcription Factor Activity
title_short Distinct Contributions of Conserved Modules to Runt Transcription Factor Activity
title_sort distinct contributions of conserved modules to runt transcription factor activity
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893994/
https://www.ncbi.nlm.nih.gov/pubmed/20462957
http://dx.doi.org/10.1091/mbc.E09-11-0953
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