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Neural crest specification and migration independently require NSD3-related lysine methyltransferase activity

Neural crest precursors express genes that cause them to become migratory, multipotent cells, distinguishing them from adjacent stationary neural progenitors in the neurepithelium. Histone methylation spatiotemporally regulates neural crest gene expression; however, the protein methyltransferases ac...

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Autores principales: Jacques-Fricke, Bridget T., Gammill, Laura S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263458/
https://www.ncbi.nlm.nih.gov/pubmed/25318671
http://dx.doi.org/10.1091/mbc.E13-12-0744
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author Jacques-Fricke, Bridget T.
Gammill, Laura S.
author_facet Jacques-Fricke, Bridget T.
Gammill, Laura S.
author_sort Jacques-Fricke, Bridget T.
collection PubMed
description Neural crest precursors express genes that cause them to become migratory, multipotent cells, distinguishing them from adjacent stationary neural progenitors in the neurepithelium. Histone methylation spatiotemporally regulates neural crest gene expression; however, the protein methyltransferases active in neural crest precursors are unknown. Moreover, the regulation of methylation during the dynamic process of neural crest migration is unclear. Here we show that the lysine methyltransferase NSD3 is abundantly and specifically expressed in premigratory and migratory neural crest cells. NSD3 expression commences before up-regulation of neural crest genes, and NSD3 is necessary for expression of the neural plate border gene Msx1, as well as the key neural crest transcription factors Sox10, Snail2, Sox9, and FoxD3, but not gene expression generally. Nevertheless, only Sox10 histone H3 lysine 36 dimethylation requires NSD3, revealing unexpected complexity in NSD3-dependent neural crest gene regulation. In addition, by temporally limiting expression of a dominant negative to migratory stages, we identify a novel, direct requirement for NSD3-related methyltransferase activity in neural crest migration. These results identify NSD3 as the first protein methyltransferase essential for neural crest gene expression during specification and show that NSD3-related methyltransferase activity independently regulates migration.
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spelling pubmed-42634582015-03-02 Neural crest specification and migration independently require NSD3-related lysine methyltransferase activity Jacques-Fricke, Bridget T. Gammill, Laura S. Mol Biol Cell Articles Neural crest precursors express genes that cause them to become migratory, multipotent cells, distinguishing them from adjacent stationary neural progenitors in the neurepithelium. Histone methylation spatiotemporally regulates neural crest gene expression; however, the protein methyltransferases active in neural crest precursors are unknown. Moreover, the regulation of methylation during the dynamic process of neural crest migration is unclear. Here we show that the lysine methyltransferase NSD3 is abundantly and specifically expressed in premigratory and migratory neural crest cells. NSD3 expression commences before up-regulation of neural crest genes, and NSD3 is necessary for expression of the neural plate border gene Msx1, as well as the key neural crest transcription factors Sox10, Snail2, Sox9, and FoxD3, but not gene expression generally. Nevertheless, only Sox10 histone H3 lysine 36 dimethylation requires NSD3, revealing unexpected complexity in NSD3-dependent neural crest gene regulation. In addition, by temporally limiting expression of a dominant negative to migratory stages, we identify a novel, direct requirement for NSD3-related methyltransferase activity in neural crest migration. These results identify NSD3 as the first protein methyltransferase essential for neural crest gene expression during specification and show that NSD3-related methyltransferase activity independently regulates migration. The American Society for Cell Biology 2014-12-15 /pmc/articles/PMC4263458/ /pubmed/25318671 http://dx.doi.org/10.1091/mbc.E13-12-0744 Text en © 2014 Jacques-Fricke and Gammill. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Jacques-Fricke, Bridget T.
Gammill, Laura S.
Neural crest specification and migration independently require NSD3-related lysine methyltransferase activity
title Neural crest specification and migration independently require NSD3-related lysine methyltransferase activity
title_full Neural crest specification and migration independently require NSD3-related lysine methyltransferase activity
title_fullStr Neural crest specification and migration independently require NSD3-related lysine methyltransferase activity
title_full_unstemmed Neural crest specification and migration independently require NSD3-related lysine methyltransferase activity
title_short Neural crest specification and migration independently require NSD3-related lysine methyltransferase activity
title_sort neural crest specification and migration independently require nsd3-related lysine methyltransferase activity
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263458/
https://www.ncbi.nlm.nih.gov/pubmed/25318671
http://dx.doi.org/10.1091/mbc.E13-12-0744
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