H3K9me3 ChIP-Seq of baboon SVZ primary cells

Histone 3 Lysine 9 (H3K9) methylation is known to be associated with pericentric heterochromatin and important in genomic stability. In this study, we show that trimethylation at H3K9 (H3K9me3) is enriched in an adult neural stem cell niche- the subventricular zone (SVZ) on the walls of the lateral ventricle in both rodent and non-human primate baboon brain. Previous studies have shown that there is significant correlation between baboon and human regarding genomic similarity and brain structure, suggesting that findings in baboon are relevant to human. To understand the function of H3K9me3 in this adult neurogenic niche, we performed genome-wide analyses using ChIP-Seq (chromatin immunoprecipitation and deep-sequencing) and RNA-Seq for in vivo SVZ cells purified from baboon brain. Through integrated analyses of ChIP-Seq and RNA-Seq, we found that H3K9me3-enriched genes associated with cellular maintenance, post-transcriptional and translational modifications, signaling pathways, and DNA replication are expressed, while genes involved in axon/neuron, hepatic stellate cell, or immune-response activation are not expressed. As neurogenesis progresses in the adult SVZ, cell fate restriction is essential to direct proper lineage commitment. Our findings highlight that H3K9me3 repression in undifferentiated SVZ cells is engaged in the maintenance of cell type integrity, implicating a role for H3K9me3 as an epigenetic mechanism to control cell fate transition within this adult germinal niche. SVZ H3K9me3 ChIP-seq profile of an adult baboon subventricular zone was generated by deep sequencing with Illumina HiSeq2000

组蛋白3赖氨酸9（Histone 3 Lysine 9, H3K9）甲基化已被证实与着丝粒异染色质相关，且对基因组稳定性具有重要意义。本研究发现，H3K9三甲基化（H3K9me3）富集于成体神经干细胞微环境——啮齿类与非人灵长类狒狒脑内侧脑室壁上的侧脑室下区（subventricular zone, SVZ）。此前研究表明，狒狒与人类在基因组相似性及脑结构方面存在显著相关性，这提示狒狒的研究发现对人类具有参考价值。为阐明H3K9me3在该成体神经发生微环境中的功能，我们针对从狒狒脑中纯化的体内侧脑室下区细胞，采用染色质免疫沉淀测序（chromatin immunoprecipitation and deep-sequencing, ChIP-Seq）与RNA测序（RNA-Seq）开展了全基因组分析。通过整合ChIP-Seq与RNA-Seq数据，我们发现富集H3K9me3的基因涉及细胞维持、转录后及翻译后修饰、信号通路与DNA复制过程，而与轴突/神经元、肝星状细胞或免疫应答激活相关的基因则未被表达。随着成体侧脑室下区的神经发生进程推进，细胞命运限制对于指导正确的谱系定向至关重要。我们的研究结果显示，未分化的侧脑室下区细胞中H3K9me3介导的基因沉默参与维持细胞类型完整性，提示H3K9me3作为一种表观遗传机制，在该成体生发微环境中调控细胞命运转变。本研究通过Illumina HiSeq2000平台深度测序，构建了成年狒狒侧脑室下区的H3K9me3 ChIP-seq图谱。