|
| Status |
Public on Jan 18, 2021 |
| Title |
Novel CHD8 genomic targets identified in fetal mouse brain by in vivo Targeted DamID |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Sequencing studies of autism spectrum disorder (ASD) cases have revealed a causal role for mutations to chromatin remodeling genes. Chromodomain helicase DNA binding protein 8 (CHD8) encodes a chromatin remodeler with one of the highest de novo mutation rates in sporadic ASD. However, the relationship between CHD8 genomic function and autism-relevant biology remains poorly elucidated. CHD8 binding studies have relied on Chromatin Immunoprecipitation followed by sequencing (ChIP-seq), but these datasets exhibit significant variation. ChIP-seq has technical limitations in the context of weak or indirect protein-DNA interactions or when high-performance antibodies are unavailable. Thus, complementary approaches are needed to establish CHD8 genomic targets. Here we used Targeted DamID in utero to characterize CHD8 binding activity in the developing embryonic mouse cortex. CHD8 Targeted DamID followed by sequencing (CHD8 TaDa-seq) revealed binding at previously identified genomic targets as well as at genes sensitive to Chd8 haploinsufficiency. CHD8 TaDa-seq showed greater sensitivity for CHD8 binding near a subset of genes specific to brain development and neuron function. These studies establish TaDa-seq as a useful alternative for mapping protein-DNA interactions in vivo and provide insights into the relationship between chromatin remodeling by CHD8 and autism-relevant pathophysiology associated with CHD8 mutations.
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| |
|
| Overall design |
Targeted DamID sequencing of CHD8 binding loci via in utero electroporation of E17.5 mouse cortex.
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| |
|
| Contributor(s) |
Wade AA, van den Ameele J, Cheetham SW, Yakob R, Brand AH, Nord AS |
| Citation(s) |
34746699 |
| |
| Submission date |
Jan 17, 2021 |
| Last update date |
Nov 10, 2021 |
| Contact name |
Alex Nord |
| E-mail(s) |
asnord@ucdavis.edu
|
| Phone |
530-754-5022
|
| Organization name |
University of California, Davis
|
| Department |
Neurobiology, Physiology, & Behavior
|
| Street address |
1544 Newton Court
|
| City |
Davis |
| State/province |
CA |
| ZIP/Postal code |
95618 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL18480 |
Illumina HiSeq 1500 (Mus musculus) |
|
| Samples (7)
|
|
| Relations |
| BioProject |
PRJNA692752 |
| SRA |
SRP302125 |
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