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| Status |
Public on Jun 17, 2016 |
| Title |
TBR1 Regulates Autism Risk Genes in the Developing Neocortex |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Exome sequencing studies have identified multiple genes harboring de novo loss-of-function (LoF) variants in individuals with autism spectrum disorders (ASD), including TBR1, a master regulator of cortical development. We performed ChIP-seq for TBR1 during mouse cortical neurogenesis and show that TBR1-bound regions are enriched adjacent to ASD genes. ASD genes were also enriched among genes that are differentially expressed in Tbr1 knockouts, which together with the ChIP-seq data, suggests direct transcriptional regulation. Of the 9 ASD genes examined, 7 were misexpressed in the cortices of Tbr1 knockout mice, including 6 with increased expression in the deep cortical layers. ASD genes with adjacent cortical TBR1 ChIP-seq peaks also showed unusually low levels of LoF mutations in a reference human population and among Icelanders. We then leveraged TBR1 binding to identify an appealing subset of candidate ASD genes. Our findings highlight a TBR1-regulated network of ASD genes in the developing neocortex that are relatively intolerant to LoF mutations, indicating that these genes may play critical roles in normal cortical development.
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| Overall design |
ChIP-seq for Tbr1 on mouse whole cortex dissected from embryonic day 15.5 (E15.5) embryos
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| Contributor(s) |
Chen B, Notwell JH, Bejerano G |
| Citation(s) |
27325115 |
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| Submission date |
Jul 27, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Gill Bejerano |
| Organization name |
Stanford University
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| Department |
Developmental Biology
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| Lab |
Bejerano Lab
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| Street address |
279 Campus Drive West (MC 5329)
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| City |
Stanford |
| State/province |
California |
| ZIP/Postal code |
94305-5329 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA291070 |
| SRA |
SRP061641 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE71384_RAW.tar |
525.5 Mb |
(http)(custom) |
TAR (of BED, BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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