Deciphering the cell type-specific gene regulatory network of learning

有一种新兴的理解是，记忆的细胞相关性可能在表观遗传状态的改变中被编码，由转录因子（tf）、染色质修饰剂和重塑复合物的相互作用调节。尽管有证据表明染色质修饰参与学习和记忆过程以及几种认知障碍的病因，但很明显，我们目前只看到了冰山一角，因为像学习和记忆这样基础的基因调控网络仍远未被阐明。我们正在使用最先进的干湿实验室技术来获得体内短期和长期记忆形成背后的动态基因调控网络的第一个细胞类型特异性图像。我们的小组正在使用细胞类型特异性ChIP-seq （BiTS-ChIP）来阐明转录因子和染色质修饰因子如何协同作用调节基因及其负责记忆形成的调控元件的表观遗传状态，以及这种状态如何在老年性痴呆或疾病中发生变化。关于特定大脑区域和细胞类型中的增强子、启动子和基因使用的详细信息将使我们对学习和记忆的调节状态及其在衰老和疾病中的变化有前所未有的了解。综上所述，这些结果应该能够详细了解疾病的病因，并突出疾病预防或干预的潜在目标。

There is an emergent understanding that the cellular correlate of memory might be encoded in alterations of the epigenetic state, regulated by the interplay of transcription factors (TFs), chromatin modifiers and remodeling complexes. Despite evidence for the involvement of chromatin modifications in learning and memory processes and the etiology of several cognitive disorders, it is clear that we are currently only looking at the tip of the iceberg, as the gene regulatory network of something as fundamental as learning and memory is still far from being elucidated. We are using state of the art wet- and drylab technologies to get a first, cell type-specific picture of the dynamic gene regulatory network underlying short- and long-term memory formation in vivo. Our group is using cell type-specific ChIP-seq (BiTS-ChIP) to elucidate how the concerted action of transcription factors and chromatin modifiers regulate the epigenetic state of genes and their regulatory elements that are responsible for the formation of memory, and how this changes in senile dementia or disease.Detailed information on enhancer, promoter, and gene usage in specific brain areas and cell types will grant unprecedented insights into the regulatory state underlying learning and memory and its changes in aging and disease. Taken together, the results should permit detailed insights into disease etiology and highlight potential targets for disease prevention or intervention.