GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE128612 Query DataSets for GSE128612
Status Public on Jun 22, 2023
Title Methyl-CpG binding domain 2 (Mbd2) is an Epigenetic Regulator of Autism-Risk Genes and Cognition [Bisulfite-Seq]
Organism Mus musculus
Experiment type Methylation profiling by high throughput sequencing
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.
Overall design Pools of hippocampi from wild-type and mice hippocmapi were subjected to genome-wide bisulfite-sequencing with replicates (8-10 mice/group), in addition targeted bisulfite-sequencing from 3-5 mice/groups were done on an additional cohort
Contributor(s) Lax E, Do Carmo S, 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 20, 2019
Last update date Sep 21, 2023
Contact name Moshe Szyf
Organization name McGill University
Department Pharmacology and Therapeutics
Street address 3655 William Osler Promendae
City Montreal
State/province Quebec
ZIP/Postal code H3G 1Y6
Country Canada
Platforms (2)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL16417 Illumina MiSeq (Mus musculus)
Samples (12)
GSM3681091 WT_2
GSM3681092 WT_4
GSM3681093 Mbd2-/- 1
This SubSeries is part of SuperSeries:
GSE128829 Methyl-CpG binding domain 2 (Mbd2) is an Epigenetic Regulator of Autism-Risk Genes and Cognition
BioProject PRJNA528280
SRA SRP188968

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE128612_Differentially_methylated_CpGs_Mbd2KO_hippocampus.txt.gz 7.6 Mb (ftp)(http) TXT
GSE128612_RAW.tar 820.0 Kb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap