Chromatin Remodeler CHD7 mutated in CHARGE Syndrome Interacts with Sox10 to Regulate Timing of CNS Myelination and Remyelination [ChIP-seq]

Mutations in CHD7, encoding ATP-dependent chromodomain-helicase-DNA-binding protein 7, in CHARGE syndrome leads to multiple congenital anomalies including growth retardation, craniofacial malformations and neurological dysfunction. Currently, mechanisms underlying the CNS phenotypes remain poorly understood. Here, we show that Chd7 is a direct transcriptional target of oligodendrogenesis-promoting factors Olig2 and Brg1 and required for proper timing of CNS myelination and remyelination. Genome-occupancy analyses coupled with transcriptome profiling reveal that Chd7 cooperates with Sox10 to target the enhancers of key myelinogenic genes, and identify novel Chd7 target.CHD7基因（编码ATP依赖的染色质域解旋酶DNA结合蛋白7）发生突变，在CHARGE综合征中可引发包括生长迟缓、颅面部畸形及神经功能障碍在内的多种先天性异常。目前，中枢神经系统（Central Nervous System, CNS）表型的潜在分子机制仍不甚明确。本研究证实，Chd7是促少突胶质细胞生成因子Olig2与Brg1的直接转录靶标，且对中枢神经系统髓鞘形成与髓鞘再生的正常时序具有不可或缺的作用。基因组占位分析结合转录组谱分析结果显示，Chd7可与Sox10协同靶向关键髓鞘生成基因的增强子，并鉴定出全新的Chd7靶标。