Neural crest specification and migration independently require NSD3-related lysine methyltransferase activity.
Bottom Line: 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.
Affiliation: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455.Show MeSH
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Mentions: NSD3 is a SET-domain lysine methyltransferase (Angrand et al., 2001; Kim et al., 2006; Li et al., 2009). In other lysine methyltransferases, mutation or deletion of the SET domain results in dominant-negative activity (Roopra et al., 2004; Lee et al., 2005; Houston et al., 2008; Huang, 2008; Joshi et al., 2008; Tanaka et al., 2008; Fujiki et al., 2009). To create a dominant negative and investigate a role for NSD3 in neural crest development, we truncated NSD3 at the start of the SET domain (NSD3Δ1707, Figure 2A) and drove expression with the green fluorescent protein (GFP) bicistronic expression plasmid pMES (Swartz et al., 2001).
Affiliation: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455.