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

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...

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Autores principales:	A. Ayanna Wade, Jelle van den Ameele, Seth W. Cheetham, Rebecca Yakob, Andrea H. Brand, Alex S. Nord
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Genomics Molecular neuroscience Biotechnology Genomic analysis Science Q
Acceso en línea:	https://doaj.org/article/4d31afdb8ce6460180b433cbe96604ab
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spelling	oai:doaj.org-article:4d31afdb8ce6460180b433cbe96604ab2021-11-20T05:08:39ZIn vivo targeted DamID identifies CHD8 genomic targets in fetal mouse brain2589-004210.1016/j.isci.2021.103234https://doaj.org/article/4d31afdb8ce6460180b433cbe96604ab2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221012025https://doaj.org/toc/2589-0042Summary: 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.A. Ayanna WadeJelle van den AmeeleSeth W. CheethamRebecca YakobAndrea H. BrandAlex S. NordElsevierarticleGenomicsMolecular neuroscienceBiotechnologyGenomic analysisScienceQENiScience, Vol 24, Iss 11, Pp 103234- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genomics Molecular neuroscience Biotechnology Genomic analysis Science Q
spellingShingle	Genomics Molecular neuroscience Biotechnology Genomic analysis Science Q A. Ayanna Wade Jelle van den Ameele Seth W. Cheetham Rebecca Yakob Andrea H. Brand Alex S. Nord In vivo targeted DamID identifies CHD8 genomic targets in fetal mouse brain
description	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.
format	article
author	A. Ayanna Wade Jelle van den Ameele Seth W. Cheetham Rebecca Yakob Andrea H. Brand Alex S. Nord
author_facet	A. Ayanna Wade Jelle van den Ameele Seth W. Cheetham Rebecca Yakob Andrea H. Brand Alex S. Nord
author_sort	A. Ayanna Wade
title	In vivo targeted DamID identifies CHD8 genomic targets in fetal mouse brain
title_short	In vivo targeted DamID identifies CHD8 genomic targets in fetal mouse brain
title_full	In vivo targeted DamID identifies CHD8 genomic targets in fetal mouse brain
title_fullStr	In vivo targeted DamID identifies CHD8 genomic targets in fetal mouse brain
title_full_unstemmed	In vivo targeted DamID identifies CHD8 genomic targets in fetal mouse brain
title_sort	in vivo targeted damid identifies chd8 genomic targets in fetal mouse brain
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/4d31afdb8ce6460180b433cbe96604ab
work_keys_str_mv	AT aayannawade invivotargeteddamididentifieschd8genomictargetsinfetalmousebrain AT jellevandenameele invivotargeteddamididentifieschd8genomictargetsinfetalmousebrain AT sethwcheetham invivotargeteddamididentifieschd8genomictargetsinfetalmousebrain AT rebeccayakob invivotargeteddamididentifieschd8genomictargetsinfetalmousebrain AT andreahbrand invivotargeteddamididentifieschd8genomictargetsinfetalmousebrain AT alexsnord invivotargeteddamididentifieschd8genomictargetsinfetalmousebrain
_version_	1718419538902515712

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

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