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Contextual interactions determine whether the Drosophila homeodomain protein, Vnd, acts as a repressor or activator

At the molecular level, members of the NKx2.2 family of transcription factors establish neural compartment boundaries by repressing the expression of homeobox genes specific for adjacent domains [Muhr et al. (2001) Cell, 104, 861–873; Weiss et al. (1998) Genes Dev., 12, 3591–3602]. The Drosophila ho...

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Autores principales: Yu, Zhongxin, Syu, Li-Jyun, Mellerick, Dervla M.
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC546129/
https://www.ncbi.nlm.nih.gov/pubmed/15640442
http://dx.doi.org/10.1093/nar/gki140
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author Yu, Zhongxin
Syu, Li-Jyun
Mellerick, Dervla M.
author_facet Yu, Zhongxin
Syu, Li-Jyun
Mellerick, Dervla M.
author_sort Yu, Zhongxin
collection PubMed
description At the molecular level, members of the NKx2.2 family of transcription factors establish neural compartment boundaries by repressing the expression of homeobox genes specific for adjacent domains [Muhr et al. (2001) Cell, 104, 861–873; Weiss et al. (1998) Genes Dev., 12, 3591–3602]. The Drosophila homologue, vnd, interacts genetically with the high-mobility group protein, Dichaete, in a manner suggesting co-operative activation [Zhao and Skeath (2002) Development, 129, 1165–1174]. However, evidence for direct interactions and transcriptional activation is lacking. Here, we present molecular evidence for the interaction of Vnd and Dichaete that leads to the activation of target gene expression. Two-hybrid interaction assays indicate that Dichaete binds the Vnd homeodomain, and additional Vnd sequences stabilize this interaction. In addition, Vnd has two activation domains that are typically masked in the intact protein. Whether vnd can activate or repress transcription is context-dependent. Full-length Vnd, when expressed as a Gal4 fusion protein, acts as a repressor containing multiple repression domains. A divergent domain in the N-terminus, not found in vertebrate Vnd-like proteins, causes the strongest repression. The co-repressor, Groucho, enhances Vnd repression, and these two proteins physically interact. The data presented indicate that the activation and repression domains of Vnd are complex, and whether Vnd functions as a transcriptional repressor or activator depends on both intra- and inter-molecular interactions.
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spelling pubmed-5461292005-02-07 Contextual interactions determine whether the Drosophila homeodomain protein, Vnd, acts as a repressor or activator Yu, Zhongxin Syu, Li-Jyun Mellerick, Dervla M. Nucleic Acids Res Article At the molecular level, members of the NKx2.2 family of transcription factors establish neural compartment boundaries by repressing the expression of homeobox genes specific for adjacent domains [Muhr et al. (2001) Cell, 104, 861–873; Weiss et al. (1998) Genes Dev., 12, 3591–3602]. The Drosophila homologue, vnd, interacts genetically with the high-mobility group protein, Dichaete, in a manner suggesting co-operative activation [Zhao and Skeath (2002) Development, 129, 1165–1174]. However, evidence for direct interactions and transcriptional activation is lacking. Here, we present molecular evidence for the interaction of Vnd and Dichaete that leads to the activation of target gene expression. Two-hybrid interaction assays indicate that Dichaete binds the Vnd homeodomain, and additional Vnd sequences stabilize this interaction. In addition, Vnd has two activation domains that are typically masked in the intact protein. Whether vnd can activate or repress transcription is context-dependent. Full-length Vnd, when expressed as a Gal4 fusion protein, acts as a repressor containing multiple repression domains. A divergent domain in the N-terminus, not found in vertebrate Vnd-like proteins, causes the strongest repression. The co-repressor, Groucho, enhances Vnd repression, and these two proteins physically interact. The data presented indicate that the activation and repression domains of Vnd are complex, and whether Vnd functions as a transcriptional repressor or activator depends on both intra- and inter-molecular interactions. Oxford University Press 2005 2005-01-07 /pmc/articles/PMC546129/ /pubmed/15640442 http://dx.doi.org/10.1093/nar/gki140 Text en © 2005, the authors Nucleic Acids Research, Vol. 33 No. 1 © Oxford University Press 2005; all rights reserved
spellingShingle Article
Yu, Zhongxin
Syu, Li-Jyun
Mellerick, Dervla M.
Contextual interactions determine whether the Drosophila homeodomain protein, Vnd, acts as a repressor or activator
title Contextual interactions determine whether the Drosophila homeodomain protein, Vnd, acts as a repressor or activator
title_full Contextual interactions determine whether the Drosophila homeodomain protein, Vnd, acts as a repressor or activator
title_fullStr Contextual interactions determine whether the Drosophila homeodomain protein, Vnd, acts as a repressor or activator
title_full_unstemmed Contextual interactions determine whether the Drosophila homeodomain protein, Vnd, acts as a repressor or activator
title_short Contextual interactions determine whether the Drosophila homeodomain protein, Vnd, acts as a repressor or activator
title_sort contextual interactions determine whether the drosophila homeodomain protein, vnd, acts as a repressor or activator
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC546129/
https://www.ncbi.nlm.nih.gov/pubmed/15640442
http://dx.doi.org/10.1093/nar/gki140
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