Methyl-CpG binding domain 2 (Mbd2) is an epigenetic regulator of autism-risk genes and cognition.

Publication date: Jul 13, 2023

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 brains of Autism Spectrum Disorder (ASD) individuals. Notably, downregulated 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. Hippocampal Mbd2 knockdown partially recapitulates the behavioral phenotypes observed in Mbd2-/- mice. These findings suggest that 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 individuals.

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Concepts Keywords
Autism Asd
Genome Autism
Hundreds Binding
Mice Binds
Neurodevelopmental Cpg


Type Source Name
disease MESH autism
disease MESH neurodevelopmental disorders
disease MESH cancer
pathway REACTOME DNA methylation
disease MESH Autism Spectrum Disorder
disease MESH abnormalities
disease MESH causes
disease MESH Rett syndrome
disease MESH MECP2 duplication syndrome
disease MESH schizophrenia
disease MESH bipolar disorder
disease MESH Pitt Hopkins syndrome
disease MESH syndrome
disease MESH Schinzel Giedion syndrome
disease MESH Liver Diseases
drug DRUGBANK Coenzyme M
drug DRUGBANK Water
disease MESH weight gain
drug DRUGBANK Formaldehyde
drug DRUGBANK Glycine
drug DRUGBANK Potassium Chloride
drug DRUGBANK Sodium lauryl sulfate
drug DRUGBANK Tromethamine
pathway KEGG Axon guidance
pathway KEGG RNA polymerase
pathway KEGG Chemical carcinogenesis
drug DRUGBANK Trestolone
pathway KEGG Ribosome

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