Chromatin Remodeler CHD7 mutated in CHARGE Syndrome Interacts with Sox10 to Regulate Timing of CNS Myelination and Remyelination [RNA-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. 4 RNA-Seq samples from P8 spinal cords of Ctrl and Chd7 cKO mice (duplicates, Ctrl and cKO)编码ATP依赖型染色质域螺旋酶DNA结合蛋白7（ATP-dependent chromodomain-helicase-DNA-binding protein 7）的CHD7基因突变可诱发CHARGE综合征，引发生长迟缓、颅面部畸形及神经功能障碍等多种先天性异常。目前，中枢神经系统（Central Nervous System, CNS）相关表型的潜在分子机制仍未被充分阐明。本研究证实，Chd7是促进少突胶质细胞生成的调控因子Olig2与Brg1的直接转录靶点，且对中枢神经系统髓鞘形成与髓鞘再生的正常时序发挥关键作用。全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，并鉴定出新型Chd7调控靶点。本次实验共设置4个RNA测序（RNA-Seq）样本，均取自出生后第8天（P8）的对照组（Ctrl）与Chd7条件性敲除（conditional knockout, cKO）小鼠的脊髓组织，其中对照组与敲除组各设2个生物学重复。