Genomics Division, MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Cell. 2013 Feb 14;152(4):895-908. doi: 10.1016/j.cell.2012.12.041. Epub 2013 Jan 31.
The mammalian telencephalon plays critical roles in cognition, motor function, and emotion. Though many of the genes required for its development have been identified, the distant-acting regulatory sequences orchestrating their in vivo expression are mostly unknown. Here, we describe a digital atlas of in vivo enhancers active in subregions of the developing telencephalon. We identified more than 4,600 candidate embryonic forebrain enhancers and studied the in vivo activity of 329 of these sequences in transgenic mouse embryos. We generated serial sets of histological brain sections for 145 reproducible forebrain enhancers, resulting in a publicly accessible web-based data collection comprising more than 32,000 sections. We also used epigenomic analysis of human and mouse cortex tissue to directly compare the genome-wide enhancer architecture in these species. These data provide a primary resource for investigating gene regulatory mechanisms of telencephalon development and enable studies of the role of distant-acting enhancers in neurodevelopmental disorders.
哺乳动物端脑在认知、运动功能和情绪中起着关键作用。尽管已经确定了其发育所需的许多基因，但协调它们体内表达的远距离作用的调节序列在很大程度上仍是未知的。在这里，我们描述了一个在发育中的端脑亚区中具有活性的体内增强子的数字图谱。我们鉴定了超过 4600 个候选胚胎前脑增强子，并研究了其中 329 个序列在转基因小鼠胚胎中的体内活性。我们为 145 个可重复的前脑增强子生成了一系列连续的组织学脑切片，从而生成了一个包含超过 32000 个切片的可公开访问的基于网络的数据集合。我们还使用人类和小鼠皮层组织的表观基因组分析直接比较了这两个物种的全基因组增强子结构。这些数据为研究端脑发育的基因调控机制提供了主要资源，并能够研究远距离作用的增强子在神经发育障碍中的作用。
