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.

中文翻译：

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赖氨酸甲基转移酶SETD2是早期神经嵴发育的动态表达调节剂

SETD2 是一种组蛋白 H3 赖氨酸 36 (H3K36) 三甲基化酶，可响应神经嵴诱导而上调。因为 H3K36 二甲基化酶 NSD3 和细胞质非组蛋白甲基化是神经嵴发育所必需的，我们研究了神经嵴中 SETD2 的表达和需求。SetD2从原肠胚形成开始在整个鸡胚层中表达。随后，SetD2mRNA 被限制在神经板中，当神经组织被区域化并做出细胞命运决定时，它在那里强烈而动态地表达。这包括在迁移前被下调的迁移前神经嵴细胞中的表达。可能由于其表达的早期开始，SETD2 morpholino 敲低不会显着改变迁移前Sox10表达或神经嵴迁移；然而，两者都被甲基转移酶突变体 SETD2 构建体破坏。这些结果表明SETD2活性对于早期神经嵴发育至关重要，进一步证明赖氨酸甲基化是调节神经嵴的重要机制。