Tien Chih-Liang, Jones Amanda, Wang Hengbin, Gerigk Magda, Nozell Susan, Chang Chenbei
Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, 1720 2nd Avenue S., Birmingham, AL 35294, USA.
Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, 1720 2nd Avenue S., Birmingham, AL 35294, USA.
Development. 2015 Feb 15;142(4):722-31. doi: 10.1242/dev.111997. Epub 2015 Jan 23.
Neural crest cells arise from the border of the neural plate and epidermal ectoderm, migrate extensively and differentiate into diverse cell types during vertebrate embryogenesis. Although much has been learnt about growth factor signals and gene regulatory networks that regulate neural crest development, limited information is available on how epigenetic mechanisms control this process. In this study, we show that Polycomb repressive complex 2 (PRC2) cooperates with the transcription factor Snail2/Slug to modulate neural crest development in Xenopus. The PRC2 core components Eed, Ezh2 and Suz12 are expressed in the neural crest cells and are required for neural crest marker expression. Knockdown of Ezh2, the catalytic subunit of PRC2 for histone H3K27 methylation, results in defects in neural crest specification, migration and craniofacial cartilage formation. EZH2 interacts directly with Snail2, and Snail2 fails to expand the neural crest domains in the absence of Ezh2. Chromatin immunoprecipitation analysis shows that Snail2 regulates EZH2 occupancy and histone H3K27 trimethylation levels at the promoter region of the Snail2 target E-cadherin. Our results indicate that Snail2 cooperates with EZH2 and PRC2 to control expression of the genes important for neural crest specification and migration during neural crest development.
神经嵴细胞起源于神经板和表皮外胚层的边界，在脊椎动物胚胎发育过程中广泛迁移并分化为多种细胞类型。尽管人们已经对调控神经嵴发育的生长因子信号和基因调控网络有了很多了解，但关于表观遗传机制如何控制这一过程的信息却有限。在本研究中，我们发现多梳抑制复合物2（PRC2）与转录因子Snail2/Slug协同作用，以调节非洲爪蟾的神经嵴发育。PRC2的核心成分Eed、Ezh2和Suz12在神经嵴细胞中表达，并且是神经嵴标志物表达所必需的。敲低PRC2中负责组蛋白H3K27甲基化的催化亚基Ezh2，会导致神经嵴特化、迁移和颅面软骨形成出现缺陷。EZH2直接与Snail2相互作用，并且在没有Ezh2的情况下，Snail2无法扩展神经嵴区域。染色质免疫沉淀分析表明，Snail2调节EZH2在其靶标E-钙黏蛋白启动子区域的占据情况以及组蛋白H3K27三甲基化水平。我们的结果表明，Snail2与EZH2和PRC2协同作用，以控制神经嵴发育过程中对神经嵴特化和迁移重要的基因的表达。
