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The Him Gene Reveals a Balance of Inputs Controlling Muscle Differentiation in Drosophila

Tissue development requires the controlled regulation of cell-differentiation programs. In muscle, the Mef2 transcription factor binds to and activates the expression of many genes and has a major positive role in the orchestration of differentiation [1–4]. However, little is known about how Mef2 ac...

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Detalles Bibliográficos
Autores principales: Liotta, David, Han, Jun, Elgar, Stuart, Garvey, Clare, Han, Zhe, Taylor, Michael V.
Formato: Texto
Lenguaje:English
Publicado: Cell Press 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1955682/
https://www.ncbi.nlm.nih.gov/pubmed/17702578
http://dx.doi.org/10.1016/j.cub.2007.07.039
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author Liotta, David
Han, Jun
Elgar, Stuart
Garvey, Clare
Han, Zhe
Taylor, Michael V.
author_facet Liotta, David
Han, Jun
Elgar, Stuart
Garvey, Clare
Han, Zhe
Taylor, Michael V.
author_sort Liotta, David
collection PubMed
description Tissue development requires the controlled regulation of cell-differentiation programs. In muscle, the Mef2 transcription factor binds to and activates the expression of many genes and has a major positive role in the orchestration of differentiation [1–4]. However, little is known about how Mef2 activity is regulated in vivo during development. Here, we characterize a gene, Holes in muscle (Him), which our results indicate is part of this control in Drosophila. Him expression rapidly declines as embryonic muscle differentiates, and consistent with this, Him overexpression inhibits muscle differentiation. This inhibitory effect is suppressed by mef2, implicating Him in the mef2 pathway. We then found that Him downregulates the transcriptional activity of Mef2 in both cell culture and in vivo. Furthermore, Him protein binds Groucho, a conserved, transcriptional corepressor, through a WRPW motif and requires this motif and groucho function to inhibit both muscle differentiation and Mef2 activity during development. Together, our results identify a mechanism that can inhibit muscle differentiation in vivo. We conclude that a balance of positive and negative inputs, including Mef2, Him, and Groucho, controls muscle differentiation during Drosophila development and suggest that one outcome is to hold developing muscle cells in a state with differentiation genes poised to be expressed.
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spelling pubmed-19556822007-08-30 The Him Gene Reveals a Balance of Inputs Controlling Muscle Differentiation in Drosophila Liotta, David Han, Jun Elgar, Stuart Garvey, Clare Han, Zhe Taylor, Michael V. Curr Biol Report Tissue development requires the controlled regulation of cell-differentiation programs. In muscle, the Mef2 transcription factor binds to and activates the expression of many genes and has a major positive role in the orchestration of differentiation [1–4]. However, little is known about how Mef2 activity is regulated in vivo during development. Here, we characterize a gene, Holes in muscle (Him), which our results indicate is part of this control in Drosophila. Him expression rapidly declines as embryonic muscle differentiates, and consistent with this, Him overexpression inhibits muscle differentiation. This inhibitory effect is suppressed by mef2, implicating Him in the mef2 pathway. We then found that Him downregulates the transcriptional activity of Mef2 in both cell culture and in vivo. Furthermore, Him protein binds Groucho, a conserved, transcriptional corepressor, through a WRPW motif and requires this motif and groucho function to inhibit both muscle differentiation and Mef2 activity during development. Together, our results identify a mechanism that can inhibit muscle differentiation in vivo. We conclude that a balance of positive and negative inputs, including Mef2, Him, and Groucho, controls muscle differentiation during Drosophila development and suggest that one outcome is to hold developing muscle cells in a state with differentiation genes poised to be expressed. Cell Press 2007-08-21 /pmc/articles/PMC1955682/ /pubmed/17702578 http://dx.doi.org/10.1016/j.cub.2007.07.039 Text en . https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license
spellingShingle Report
Liotta, David
Han, Jun
Elgar, Stuart
Garvey, Clare
Han, Zhe
Taylor, Michael V.
The Him Gene Reveals a Balance of Inputs Controlling Muscle Differentiation in Drosophila
title The Him Gene Reveals a Balance of Inputs Controlling Muscle Differentiation in Drosophila
title_full The Him Gene Reveals a Balance of Inputs Controlling Muscle Differentiation in Drosophila
title_fullStr The Him Gene Reveals a Balance of Inputs Controlling Muscle Differentiation in Drosophila
title_full_unstemmed The Him Gene Reveals a Balance of Inputs Controlling Muscle Differentiation in Drosophila
title_short The Him Gene Reveals a Balance of Inputs Controlling Muscle Differentiation in Drosophila
title_sort him gene reveals a balance of inputs controlling muscle differentiation in drosophila
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1955682/
https://www.ncbi.nlm.nih.gov/pubmed/17702578
http://dx.doi.org/10.1016/j.cub.2007.07.039
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