摘要：SummaryGenetic studies of autism have revealed causal roles for chromatin remodeling gene mutations. Chromodomain helicase DNA binding protein 8 (CHD8) encodes a chromatin remodeler with significantde novomutation rates in sporadic autism. However, relationships between CHD8 genomic function and autism-relevant biology remain poorly elucidated. Published studies utilizing ChIP-seq to map CHD8 protein-DNA interactions have high variability, consistent with technical challenges and limitations associated with this method. Thus, complementary approaches are needed to establish CHD8 genomic targets and regulatory functions in developing brain. We usedin uteroCHD8 Targeted DamID followed by sequencing (TaDa-seq) to characterize CHD8 binding in embryonic mouse cortex. CHD8 TaDa-seq reproduced interaction patterns observed from ChIP-seq and further highlighted CHD8 distal interactions associated with neuronal loci. This study establishes TaDa-seq as a useful alternative for mapping protein-DNA interactionsin vivoand provides insights into the regulatory targets of CHD8 and autism-relevant pathophysiology associated withCHD8mutations.Graphical abstractDisplay OmittedHighlights•ChIP-seq maps protein-DNA interactions but can have significant technical limitations•DamID maps protein-DNA interactions using genome-wide DNA adenine methylation signals•We used Targeted DamIDin vivoin embryonic mouse brain to map CHD8 interactions•TaDa-seq resolved neurodevelopmental CHD8 interactions at promoters and enhancersGenomics; Molecular neuroscience; Biotechnology; Genomic analysis
