REST ChIP-seq in human and mouse hippocampus

The transcriptional repressor REST (RE1 Silencing Transcription Factor) is a master regulator of thousands of neuronal genes that together impart the terminally differentiated neuronal phenotype. Because of this unique feature, REST has been, and continues to be, a widely used model for understanding neurogenesis and neuronal cell function. These studies have focused primarily on murine embryonic development, but recent studies have pointed to distinct postnatal roles for REST in stroke, epilepsy, aging and cognitive decline. The function of REST in healthy human brain tissue, however, still remains poorly characterized. Here, we present deep sequencing chromatin immunoprecipitation evidence for divergent REST function in normal mouse and human postmortem adult hippocampus. In mouse, REST occupies only 221 peaks that are divided between prototypical REST target genes shared with non-neuronal cells, as well as peaks unique to the hippocampus. Surprisingly, the mouse hippocampal-unique sites are not conserved in human, which contains 1886 REST peaks unique to the hippocampus. Further, the REST peaks unique to the hippocampus represent a potentially new category of target genes encoding proteins important in the immune response. Our results suggest the possibility that REST protects against aberrant immunological responses during normal human aging and that mouse may not model this aging function. Examination of REST-bound regions in post-mertem tissue from human and mouse hippocampus

转录抑制因子REST（RE1沉默转录因子，RE1 Silencing Transcription Factor）是数千个神经元基因的核心调控因子，这些基因共同介导终末分化的神经元表型。凭借这一独特特性，REST既往是、且至今仍是解析神经发生与神经元细胞功能的经典研究模型。现有相关研究多聚焦于小鼠胚胎发育过程，但近期研究揭示了REST在脑卒中、癫痫、衰老及认知衰退中发挥的独特产后调控作用。然而，REST在健康人类脑组织中的功能仍未得到充分阐释。本研究提供了正常小鼠与人类死后成人海马组织中REST功能存在分化的深度测序染色质免疫沉淀实验证据。在小鼠体内，REST仅结合221个峰位，这些峰位可分为两类：与非神经元细胞共享的典型REST靶基因相关区域，以及海马组织特异性结合峰位。令人意外的是，小鼠海马组织特异性结合位点在人类中并不保守；人类海马组织中存在1886个REST特异性结合峰位。进一步分析显示，海马组织特异性REST结合峰位对应一类潜在的新型靶基因，其编码的蛋白在免疫应答中发挥重要功能。本研究结果提示，REST或可在人类正常衰老过程中抵御异常免疫应答，而小鼠模型可能无法复现这一衰老相关调控功能。对人类与小鼠海马组织死后样本中的REST结合区域的分析。