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DNA methylation in frontal cortex of Setd1a haploinsufficient mice

ABSTRACT: DNA methylation in frontal cortex of Setd1a haploinsufficient mice

PROVIDER: PRJNA1252450 | ENA |

REPOSITORIES: ENA

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DNA methylation in frontal cortex of Setd1a haploinsufficient mice

Project description:SETD1A, a histone methyltransferase, is implicated in schizophrenia through rare loss-of-function mutations. While SETD1A regulates gene expression via histone H3K4 methylation, its influence on broader epigenetic dysregulation remains incompletely understood. We explored the hypothesis that SETD1A haploinsufficiency contributes to neurodevelopmental disruptions associated with schizophrenia risk via alterations in DNA methylation. We profiled DNA methylation in the frontal cortex of Setd1a+/- mice across prenatal and postnatal development using Illumina Mouse Methylation arrays. Differentially methylated positions and regions were identified, and their functional relevance examined through gene and biological annotation. We integrated these findings with transcriptomic and proteomics datasets, and assessed mitochondrial complex I activity to explore potential downstream functional effects. Setd1a haploinsufficiency resulted in widespread hypomethylation of genes related to ribosomal function and RNA processing that persisted across all developmental stages. Setd1a-targeted promoter regions and noncoding small nucleolar RNAs (snoRNAs) were also enriched for differentially methylated sites. Despite the downregulation of mitochondrial gene expression, the same genes were not differentially methylated and complex I activity in Setd1a+/- mice did not differ significantly from controls. Genes overlapping hypomethylated regions were enriched for common genetic associations with schizophrenia. Our findings suggest that SETD1A haploinsufficiency disrupts the epigenetic regulation of ribosomal pathways. These results provide insight into an alternative mechanism through which genetic variation in SETD1A influences developmental and synaptic plasticity, contributing to schizophrenia pathophysiology.

2025-04-22 | GSE295008 | GEO

DNA methylation data from human liver, frontal cortex, spleen and colon

Project description:DNA methylation data from human tissues: 5 samples each of normal liver, frontal cortex, spleen and colon. 5 samples of colon tumor. Genomic DNA was isolated and hybridized to custom-designed Nimblegen microarrays (CHARM human array v1). 4 normal tissues and 1 colon tumor

2010-08-28 | E-GEOD-23841 | biostudies-arrayexpress

DNA methylation data from human liver, frontal cortex, spleen and colon

Project description:DNA methylation data from human tissues: 5 samples each of normal liver, frontal cortex, spleen and colon. 5 samples of colon tumor.

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Proteomic analysis of somatosensory cortex of Pten haploinsufficient mice

Project description:To discover differentially expressed proteins in somatosensory cortex of Pten haploinsufficient mice at adolescence (P30). Result reveals signatures of perturbation of dendritic spine development, keratinization and hamartoma. These are collectively respresentating molecular perturbation of neuropathology of PTEN Harmatoma Tumor Syndrome (PHTS).

2023-04-26 | PXD030573 | Pride

Parkinson Disease Frontal Cortex Transcriptomic analysis

Project description:Parkinson Disease Frontal Cortex Transcriptomic analysis

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Parkinson Disease Frontal Cortex ncRNA Profiling

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Transcriptome Alterations in Myotonic Dystrophy Frontal Cortex

Project description:Transcriptome Alterations in Myotonic Dystrophy Frontal Cortex

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Epigenome-wide association study of human frontal cortex identifies differential methylation in Lewy body pathology

Project description:The goal of the study was to investigate if DNA methylation is associated with Lewy body pathology in human brain tissue. The Illumina Infinium MethylationEPIC Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpGs in postmortem human frontal cortex samples from European donors in the Netherlands Brain Bank. Following quality checks, sample filtering and normalization, association between CpG methylation and Braak alpha-synuclein stage was assessed using linear models.

2022-07-20 | GSE203332 | GEO

Microarrays of frontal cortex (area 8) of Parkinson cases and controls

Project description:Microarrays of frontal cortex (area 8) of Parkinson cases and controls

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Mutation of a schizophrenia risk gene SETD1A alters neuronal network activity in human neurons through cAMP/PKA pathway

Project description:Using CRISPR/Cas9 to generate an hiPSC line with SETD1A haploinsufficiency and differentiating it into glutamatergic and GABAergic neurons, we found that SETD1A haploinsufficiency resulted in altered neuronal network activity, which was predominantly defined by increased network burst frequency, whereas unchanged global firing activity. In individual neurons, this network phenotype was reflected functionally by increased synchronized synaptic inputs and structurally by increased somatodendritic complexity in both glutamatergic and GABAergic neurons. The transcriptome profile in SETD1A haploinsufficient neurons demonstrated perturbations in gene sets associated with schizophrenia, synaptic transmission, and glutamatergic synaptic function. In addition, transcriptomic data suggested cAMP/PKA pathway might be disturbed in SETD1A haploinsufficient networks, which was further verified by pharmacological experiments.

2021-07-23 | GSE180648 | GEO

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