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Brain methylome remodeling sustains neuronal activity gene expression in mice exposed to maternal immune activation [5hmc]

ABSTRACT: Brain methylome remodeling sustains neuronal activity gene expression in mice exposed to maternal immune activation [5hmc]

PROVIDER: PRJNA1003538 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25573584_1.fastq.gz	Fastqsanger.gz
	SRR25573584_2.fastq.gz	Fastqsanger.gz
	SRR25573585_1.fastq.gz	Fastqsanger.gz
	SRR25573585_2.fastq.gz	Fastqsanger.gz
	SRR25573586_1.fastq.gz	Fastqsanger.gz

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Brain methylome remodeling sustains neuronal activity gene expression in mice exposed to maternal immune activation [5hmc]

Project description:Maternal infections have been linked to various neuropsychiatric disorders that may later emerge in offspring. 5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC) are key DNA modifications but their roles in maternal infection remain to be elucidated. It has been documented that Zika virus (ZIKV) infection during pregnancy leads to structural brain defects such as microcephaly in offspring. However, whether and how offspring exposed to maternal ZIKV infection develop neurocognitive complications remain largely unknown. Here we report that ZIKV infection during mouse pregnancy leads to offspring with depression- and anxiety-like behaviors, which are transmitted to the next generation. Single nucleus RNA sequencing in prefrontal cortex (PFC) of ZIKV offspring mice revealed cell type-specific gene dysregulation associated with neuropsychiatric lesions. Genome-wide 5hmC, 5mC, and transcriptome profiling in ZIKV PFC revealed an overall loss of 5hmC and an increase of 5mC in intragenic regions, associated with transcriptional changes in key functional genes. Gain-of-5hmC regions were mainly located in intergenic transposable elements (TEs) coupled with decreased 5mC and dynamic TE expression. These results provide the first 5hmC study in maternal infection and suggest that maternal ZIKV infection remodels methylome and gene expression in offspring mouse brains, contributing to transgenerational behavior changes.

2023-10-25 | GSE240415 | GEO

Brain methylome remodeling sustains neuronal activity gene expression in mice exposed to maternal immune activation [5mC]

2023-10-25 | GSE240413 | GEO

Brain methylome remodeling sustains neuronal activity gene expression in mice exposed to maternal immune activation

Project description:Brain methylome remodeling sustains neuronal activity gene expression in mice exposed to maternal immune activation

| PRJNA1003534 | ENA

Brain methylome remodeling sustains neuronal activity gene expression in mice exposed to maternal immune activation [5mC]

Project description:Brain methylome remodeling sustains neuronal activity gene expression in mice exposed to maternal immune activation [5mC]

| PRJNA1003537 | ENA

Methylome of 5mC and 5hmC regulated by NEIL2

Project description:To elucidate the role of DNA glycosylase NEIL2 in regulation of DNA methylome, we performed genome sequencing of epigenetic marker 5mC and 5hmC in genome-wide using enyme-based library methods of TAPS and CAPS. The 5mC and 5hmC profile in CpG contect was further extracted and analysed.

2023-12-13 | GSE240177 | GEO

Brain methylome remodeling sustains neuronal activity gene expression in mice exposed to maternal immune activation

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-10-25 | GSE240417 | GEO

Methylome of 5mC and 5hmC regulated by NEIL2

Project description:Methylome of 5mC and 5hmC regulated by NEIL2

| PRJNA1002410 | ENA

Brain methylome remodeling selectively regulates neuronal activity genes linking to emotional behaviors in mice exposed to maternal immune activation.

Project description:How early life experience is translated into storable epigenetic information leading to behavioral changes remains poorly understood. Here we found that Zika virus (ZIKV) induced-maternal immune activation (MIA) imparts offspring with anxiety- and depression-like behavior. By integrating bulk and single-nucleus RNA sequencing (snRNA-seq) with genome-wide 5hmC (5-hydroxymethylcytosine) profiling and 5mC (5-methylcytosine) profiling in prefrontal cortex (PFC) of ZIKV-affected male offspring mice, we revealed an overall loss of 5hmC and an increase of 5mC levels in intragenic regions, associated with transcriptional changes in neuropsychiatric disorder-related genes. In contrast to their rapid initiation and inactivation in normal conditions, immediate-early genes (IEGs) remain a sustained upregulation with enriched expression in excitatory neurons, which is coupled with increased 5hmC and decreased 5mC levels of IEGs in ZIKV-affected male offspring. Thus, MIA induces maladaptive methylome remodeling in brain and selectively regulates neuronal activity gene methylation linking to emotional behavioral abnormalities in offspring.

| S-EPMC10687003 | biostudies-literature

Rest recruits neuronal Tet3 to induce chromatin remodeling and gene expression

Project description:Ten-eleven translocation (Tet) hydroxylases (Tet1-3) oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). In neurons increased 5hmC levels within gene bodies correlate positively with gene expression. The mechanisms controlling Tet activity and 5hmC levels are poorly understood. In particular, it is not known how the neuronal Tet3 isoform lacking a DNA binding domain is targeted to the DNA. To identify factors binding to Tet3 we screened for proteins that co-precipitate with Tet3 from mouse retina and identified the transcriptional repressor Rest as a highly enriched Tet3-specific interactor. Rest was able to enhance Tet3 hydroxylase activity after co-expression and overexpression of Tet3 activated transcription of Rest-target genes. Moreover, we found that Tet3 also interacts with Nsd3 and two other H3K36 methyltransferases and is able to induce H3K36 trimethylation. We propose a mechanism for transcriptional activation in neurons that involves Rest-guided targeting of Tet3 to the DNA for directed 5hmC-generation and Nsd3-mediated H3K36 trimethylation.

2015-04-02 | PXD001857 | Pride

PCGP Dyer_iPSC 5hmc - samples

Project description:DATA FILES FOR PCGP Dyer_iPSC 5hmc

| EGAD00001001418 | EGA