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

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. Overall design: 4 RNA-Seq samples from P8 spinal cords of Ctrl and Chd7 cKO mice (duplicatess, Ctrl and cKO)

CHARGE综合征患者中，编码ATP依赖型染色质结构域解旋酶DNA结合蛋白7（ATP-dependent chromodomain-helicase-DNA-binding protein 7）的CHD7基因发生突变，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，该类中枢神经系统（CNS）表型背后的分子机制仍不甚明晰。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关键调控作用。全基因组占据分析结合转录组测序分析显示，Chd7可与Sox10协同结合关键髓鞘生成基因的增强子，并鉴定出新型Chd7靶标基因。实验设计：取自P8龄野生型（Ctrl）与Chd7条件性敲除（cKO）小鼠脊髓的4份RNA测序（RNA-Seq）样本，两组各设2次生物学重复。