In vivo targeted DamID identifies CHD8 genomic targets in fetal mouse brain
A. Ayanna Wade,
Jelle van den Ameele,
Seth W. Cheetham,
Rebecca Yakob,
Andrea H. Brand,
Alex S. Nord
Affiliations
A. Ayanna Wade
Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, CA 95616, USA; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, CA 95616, USA
Jelle van den Ameele
The Gurdon Institute and Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 1TN, UK
Seth W. Cheetham
The Gurdon Institute and Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 1TN, UK
Rebecca Yakob
The Gurdon Institute and Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 1TN, UK
Andrea H. Brand
The Gurdon Institute and Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 1TN, UK; Corresponding author
Alex S. Nord
Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, CA 95616, USA; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, CA 95616, USA; Corresponding author
Summary: Genetic studies of autism have revealed causal roles for chromatin remodeling gene mutations. Chromodomain helicase DNA binding protein 8 (CHD8) encodes a chromatin remodeler with significant de novo mutation 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 used in utero CHD8 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 interactions in vivo and provides insights into the regulatory targets of CHD8 and autism-relevant pathophysiology associated with CHD8 mutations.
