Repository logo
 

In vivo targeted DamID identifies CHD8 genomic targets in fetal mouse brain.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Wade, A Ayanna 
Van Den Ameele, Jelle  ORCID logo  https://orcid.org/0000-0002-2744-0810
Cheetham, Seth W 
Yakob, Rebecca 

Abstract

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.

Description

Keywords

Biotechnology, Genomic analysis, Genomics, Molecular neuroscience

Journal Title

iScience

Conference Name

Journal ISSN

2589-0042
2589-0042

Volume Title

24

Publisher

Elsevier BV
Sponsorship
Wellcome Trust (103792/Z/14/Z)
Wellcome Trust (105839/Z/14/Z)
Royal Society (RP150061)
Wellcome Trust (092096/Z/10/Z)
Cancer Research Uk (None)