Developmental Neurobiology Unit, Instituto de Biomedicina de Valencia IBV-CSIC, Valencia, Spain.
Departamento de Genómica y Salud, Centro Superior de Investigación en Salud Pública, FISABIO, Valencia, Spain.
Elife. 2018 Mar 22;7:e32785. doi: 10.7554/eLife.32785.
Cell differentiation is controlled by individual transcription factors (TFs) that together activate a selection of enhancers in specific cell types. How these combinations of TFs identify and activate their target sequences remains poorly understood. Here, we identify the -regulatory transcriptional code that controls the differentiation of serotonergic HSN neurons in . Activation of the HSN transcriptome is directly orchestrated by a collective of six TFs. Binding site clusters for this TF collective form a regulatory signature that is sufficient for de novo identification of HSN neuron functional enhancers. Among neurons, the HSN transcriptome most closely resembles that of mouse serotonergic neurons. Mouse orthologs of the HSN TF collective also regulate serotonergic differentiation and can functionally substitute for their worm counterparts which suggests deep homology. Our results identify rules governing the regulatory landscape of a critically important neuronal type in two species separated by over 700 million years.
细胞分化受个体转录因子 (TFs) 的控制，这些转录因子共同激活特定细胞类型中的一组增强子。这些 TF 组合如何识别和激活其靶序列仍然知之甚少。在这里，我们确定了调控 的 5-羟色胺能 HSN 神经元分化的 -调节转录码。HSN 转录组的激活是由六个 TF 集体直接协调的。这个 TF 集体的结合位点簇形成了一个调控特征，足以从头鉴定 HSN 神经元功能增强子。在 神经元中，HSN 转录组最类似于小鼠 5-羟色胺能神经元。HSN TF 集体的小鼠同源物也调节 5-羟色胺能分化，并能在功能上替代其线虫对应物，这表明存在深度同源性。我们的研究结果确定了在两个分离超过 7 亿年的物种中调控重要神经元类型的调控景观的规则。
