The lysine methyltransferase SETD2 is a dynamically expressed regulator of early neural crest development.

SETD2 is a histone H3 lysine 36 (H3K36) tri-methylase that is upregulated in response to neural crest induction. Because the H3K36 di-methylase NSD3 and cytoplasmic non-histone protein methylation are necessary for neural crest development, we investigated the expression and requirement for SETD2 in the neural crest. SetD2 is expressed throughout the chick blastoderm beginning at gastrulation. Subsequently, SetD2 mRNA becomes restricted to the neural plate, where it is strongly and dynamically expressed as neural tissue is regionalized and cell fate decisions are made. This includes expression in premigratory neural crest cells, which is downregulated prior to migration. Likely due to the early onset of its expression, SETD2 morpholino knockdown does not significantly alter premigratory Sox10 expression or neural crest migration; however, both are disrupted by a methyltransferase mutant SETD2 construct. These results suggest that SETD2 activity is essential for early neural crest development, further demonstrating that lysine methylation is an important mechanism regulating the neural crest.