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Deciphering the cell type-specific gene regulatory network of learning

破译细胞类型特异性基因调控学习网络

基本信息

批准号：
261639244
负责人：
Professor Dr. Stefan Bonn
金额：
--
依托单位：
Institut für Medizinische Systembiologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2014
资助国家：
德国
起止时间：
2013-12-31 至 2018-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/261639244?language=en
关键词：
Deciphering cell type specific gene

项目摘要

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.

有一个新兴的理解，记忆的细胞相关可能是编码的表观遗传状态的改变，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了学习和记忆过程以及几种认知障碍的病因学，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本的基因调控网络仍然远未阐明。我们正在使用最先进的湿实验室和干实验室技术，以获得体内短期和长期记忆形成的动态基因调控网络的第一个细胞类型特异性图片。我们的团队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剂的协同作用如何调节负责记忆形成的基因及其调控元件的表观遗传状态，以及这种状态在老年痴呆或疾病中如何变化。而基因在特定脑区和细胞类型中的使用，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。总之，结果应该允许详细了解疾病病因，并突出疾病预防或干预的潜在目标。