Nasal and otic placode specific regulation of Sox2 involves both activation by Sox-Sall4 synergism and multiple repression mechanisms
Nasal and otic placode specific regulation of Sox2 involves both activation by Sox-Sall4 synergism and multiple repression mechanisms
复制标题
Sox2 的鼻和耳基板特异性调节涉及 Sox-Sall4 协同作用的激活和多种抑制机制
DOI：
10.1016/j.ydbio.2017.11.005
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发表时间：
2018
影响因子：
2.7
通讯作者：
Uchikawa Masanori
中科院分区：
文献类型：
--
作者：
Sugahara Satoko;Fujimoto Tooru;Kondoh Hisato;Uchikawa Masanori
转录因子genesox2在整个感觉发育过程中表达，但调节该基因的增强子因发育阶段和组织而异。为了进一步了解基因调控网络在感觉基因位规范中的作用，我们在鸡胚胎中研究了sox2鼻部双特异性NOP1增强子的调控。利用电穿孔法进行的缺失和突变分析表明，转录抑制机制与激活机制结合决定了胎盘特异性。NOP1增强子的激活涉及与邻近位点结合的Sall4和SoxB1/SoxE因子的协同作用。抑制元件的缺失导致增强子活性的组织区域扩大到sall4和soxb1 /重叠表达的区域，例如中枢神经系统和神经嵴。在众多抑制NOP1增强子活性的抑制因子中，与Zeb/Snail家族抑制因子结合的CACCT/CACCTG基序发挥了重要作用。过表达δEF1 （Zeb1）或Snail2 （Slug）强烈抑制NOP1活性。这些数据表明，Sall4-Sox协同作用的激活和涉及Zeb/Snail因子的多种抑制机制对于sox2调控局限于鼻腔和耳部基板至关重要。
Transcription factor geneSox2is expressed throughout sensory development, but the enhancers that regulate the gene vary depending on the developmental stages and tissues. To gain new insights into the gene regulatory network in sensory placode specification, regulation of the nasal-otic bispecific NOP1 enhancer ofSox2was investigated in chicken embryos. Deletion and mutational analyses using electroporation showed that transcriptional repression mechanisms in combination with activation mechanisms determine placodal specificity. Activation of the NOP1 enhancer involves synergistic action by Sall4 and SoxB1/SoxE factors that bind to the adjacent sites. Deletion of repressive elements resulted in widening of the tissue area for enhancer activity to a region where the expression ofSall4andSoxB1/Eoverlaps, e.g., the CNS and neural crest. Among multiple repressive elements that contribute to the placodal confinement of the NOP1 enhancer activity, CACCT/CACCTG motifs bound by Zeb/Snail family repressors play important roles. Overexpression of δEF1 (Zeb1) or Snail2 (Slug) strongly inhibited NOP1 activity. These data indicate that both activation by Sall4-Sox synergism and multiple repression mechanisms involving Zeb/Snail factors are essential forSox2regulation to be confined to the nasal and otic placodes.