title: Neural crest specification and migration independently require NSD3-related lysine methyltransferase activity.
abstract: 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.
authors.affiliation: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455.
authors.forename: Bridget T
authors.initials: BT
authors.lastname: Jacques-Fricke
authors.affiliation: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455 gammi001@umn.edu.
authors.forename: Laura S
authors.initials: LS
authors.lastname: Gammill
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000502:physiology*; D019521:Body Patterning; D020134:Catalytic Domain; D002465:Cell Movement; D002642:Chick Embryo; D019175:DNA Methylation; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D011495:Histone-Lysine N-Methyltransferase / Q000502:physiology*; D009432:Neural Crest / Q000166:cytology* / Q000196:embryology; D055757:SOXE Transcription Factors / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D030161:Avian Proteins; D055757:SOXE Transcription Factors; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D011495:Histone-Lysine N-Methyltransferase