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| Status |
Public on Jun 22, 2023 |
| Title |
Methyl-CpG binding domain 2 (Mbd2) is an Epigenetic Regulator of Autism-Risk Genes and Cognition [ChIP-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The Methyl-CpG-Binding Domain Protein family has been implicated in neurodevelopmental disorders. The Methyl-CpG-binding domain 2 (Mbd2) binds methylated DNA and was shown to play an important role in cancer and immunity. Some evidence linked this protein to neurodevelopment. However, its exact role in neurodevelopment and brain function is mostly unknown. Here we show that Mbd2-deficiency in mice (Mbd2-/-) results in deficits in cognitive, social and emotional functions. Mbd2 binds regulatory DNA regions of neuronal genes in the hippocampus and loss of Mbd2 alters the expression of hundreds of genes with a robust down-regulation of neuronal gene pathways. Further, a genome-wide DNA methylation analysis found an altered DNA methylation pattern in regulatory DNA regions of neuronal genes in Mbd2-/- mice. Differentially expressed genes significantly overlap with gene-expression changes observed in brain of Autism Spectrum Disorder (ASD) individuals. Notably, down-regulated genes are significantly enriched for human ortholog ASD risk-genes. Observed hippocampal morphological abnormalities were similar to those found in individuals with ASD and ASD rodent models. Mbd2 knockdown partially recapitulates the behavioral phenotypes observed in Mbd2-/- mice. These findings suggest Mbd2 is a novel epigenetic regulator of genes that are associated with ASD in humans. Mbd2 loss causes behavioral alterations that resemble those found in ASD patients.
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| Overall design |
Pools of hippocampi from wild-type and knockout mice were subjected to Mbd2 ChIP-seq.
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| Contributor(s) |
Lax E, Carmo SD, Enuka Y, Sapozhnikov DM, Welikovitch LA, Mahmood N, Rabbani SA, Wang L, Britt JP, Hancock WW, Yarden Y, Szyf M |
| Citation(s) |
37443311 |
| |
| Submission date |
Mar 22, 2019 |
| Last update date |
Sep 21, 2023 |
| Contact name |
Moshe Szyf |
| Organization name |
McGill University
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| Department |
Pharmacology and Therapeutics
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| Street address |
3655 William Osler Promendae
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| City |
Montreal |
| State/province |
Quebec |
| ZIP/Postal code |
H3G 1Y6 |
| Country |
Canada |
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| Platforms (2) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (5)
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| This SubSeries is part of SuperSeries: |
| GSE128829 |
Methyl-CpG binding domain 2 (Mbd2) is an Epigenetic Regulator of Autism-Risk Genes and Cognition |
|
| Relations |
| BioProject |
PRJNA528585 |
| SRA |
SRP189133 |
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