Genome-wide sequencing of REST binding (ChIP-seq) in adult hippocampal neural stem cells in vitro a.k.a. HCN cells in quiescent (iQNP) and proliferative (TAP) conditions

We report the high-throughput profiling of REST binding in mammalian adult hippocampal stem cells in culture (HCN cells). By obtaining 33 to 38 million single-end reads of sequence from chromatin immunoprecipitated DNA, we generated genome-wide REST binding state of HCN cells in induced quiescent (iQNP) and proliferating (TAP) conditions. Thereafter, we annotated the peaks to genomic regions and associated genes. We find that with +/-10kb of transcription start site of genes, REST efficiently binds neuronal genes and represses them in HCN cells in both iQNP and TAP conditions. Moreover, only in the iQNP REST also binds non-neuronal genes like DNA replication genes. This study reveals that in addition to its well known function as a neuronal repressor in non-neuronal tissue, REST can also play other diverse roles in non-neuronal tissues.本研究报道了培养体系中哺乳动物成年海马干细胞（HCN细胞，HCN cells）的阻遏元件1沉默转录因子（REST，Repressor Element 1 Silencing Transcription Factor）结合的高通量谱分析。通过对染色质免疫沉淀所得DNA进行测序，获取3300万至3800万条单端测序读段，我们构建了HCN细胞在诱导静止态（iQNP）与增殖态（TAP）两种培养条件下的全基因组REST结合状态图谱。随后，我们将测序结合峰注释至基因组区域及其关联基因。研究发现，在基因转录起始位点（transcription start site）上下游10kb范围内，REST在iQNP和TAP两种条件下的HCN细胞中均能高效结合神经元基因并对其产生转录抑制作用。此外，仅在诱导静止态下，REST还可结合DNA复制基因等非神经元基因。本研究揭示，除其在非神经元组织中作为神经元基因阻遏因子的经典已知功能外，REST在非神经元组织中还可发挥其他多样化的调控作用。