One of the earliest patterning events in the vertebrate neural plate is the specification of mes/r1, the territory comprising the prospective mesencephalon and the first hindbrain rhombomere. Within mes/r1, an interface of gene expression defines the midbrain–hindbrain boundary (MHB), a lineage restriction that separates the mesencephalon and rhombencephalon. wnt1 is critical to mes/r1 development and functions within the MHB as a component of the MHB gene regulatory network (GRN). Despite its importance to these critical and early steps of vertebrate neurogenesis, little is known about the factors responsible for wnt1 transcriptional regulation. In the zebrafish, wnt1 and its neighboring paralog, wnt10b, are expressed in largely overlapping patterns, suggesting co-regulation. To understand wnt1 and wnt10b transcriptional control, we used a comparative genomics approach to identify relevant enhancers. We show that the wnt1-wnt10b locus contains multiple cis-regulatory elements that likely interact to generate the wnt1 and wnt10b expression patterns. Two of 11 conserved enhancers tested show activity restricted to the midbrain and MHB, an activity that is conserved in the distantly related spotted gar orthologous elements. Three non-conserved elements also play a likely role in wnt1 regulation. The identified enhancers display dynamic modes of chromatin accessibility, suggesting controlled deployment during embryogenesis. Our results suggest that the control of wnt1 and wnt10b expression is under complex regulation involving the interaction of multiple enhancers.

中文翻译：

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对wnt1调控染色体景观的分析。

脊椎动物神经板中最早的构图事件之一是mes / r1的规范，该领域包括预期的中脑和第一个后脑菱形。在mes / r1中，基因表达的界面定义了中脑-后脑边界（MHB），这是将中脑和横脑分开的谱系限制。wnt1对mes / r1的发展至关重要，并且在MHB中作为MHB基因调控网络（GRN）的一部分起作用。尽管它对脊椎动物神经发生的这些关键和早期步骤很重要，但对负责wnt1转录调控的因素知之甚少。在斑马鱼中，wnt1及其附近的旁系同源物，wnt10b，在很大程度上重叠的模式表示，表明共同监管。为了了解wnt1和wnt10b转录调控，我们使用了比较基因组学方法来鉴定相关的增强子。我们显示wnt1-wnt10b基因座包含多个顺式调控元件，可能相互作用以生成wnt1和wnt10b表达模式。在测试的11个保守增强剂中，有两个显示出活性仅限于中脑和MHB，而在远距离相关的斑点ous直系同源元件中则是保守的。三个非保守元素也可能在wnt1中起作用规。鉴定出的增强子显示出染色质可及性的动态模式，表明在胚胎发生过程中受控制的部署。我们的结果表明，对wnt1和wnt10b表达的控制处于复杂的调控之下，涉及多个增强子的相互作用。