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DNA methyltransferase inhibition induces dynamic gene expression changes in lung CD4+ T cells of neonatal mice with E. coli pneumonia

ABSTRACT: DNA methyltransferase inhibition induces dynamic gene expression changes in lung CD4+ T cells of neonatal mice with E. coli pneumonia

PROVIDER: PRJNA885509 | ENA |

REPOSITORIES: ENA

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DNA methyltransferase inhibition induces dynamic gene expression changes in lung CD4+ T cells of neonatal mice with E. coli pneumonia [RRBS]

Project description:Bacterial pulmonary infections are a major cause of morbidity and mortality in neonates, with less severity in older children (juveniles). Previous studies demonstrated that CD4+ T cells in the mouse lung, whose primary responsibility is coordinating the immune response foreign pathogens, are differentially methylated in neonates compared with juveniles. Nevertheless, the effect of this differential methylation on CD4+ T cell gene expression and response to infection remains unclear. We treated E. coli-infected neonatal (4-day-old) and juvenile (13-day-old) mice with decitabine (DAC), a DNA methyltransferase inhibitor with broad-spectrum DNA demethylating activity, and performed simultaneous genome-wide DNA methylation and transcriptional profiling on lung CD4+ T cells. Juvenile and neonatal mice experienced differential demethylation in response to DAC treatment, with larger methylation differences observed in neonates. By cross-filtering differentially expressed genes between juveniles and neonates with those sites that were demethylated in neonates, we found that interferon-responsive genes such as Ifit1 are the most down-regulated methylation-sensitive genes in neonatal mice. DAC treatment shifted neonatal lung CD4+ T cells toward a gene expression program similar to that of juveniles. Following lung infection with E. coli, lung CD4+ T cells in neonatal mice exhibit epigenetic repression of important host defense pathways, which are activated by inhibition of DNA methyltransferase activity to resemble a more mature profile.

2022-12-22 | GSE214488 | GEO

DNA methyltransferase inhibition induces dynamic gene expression changes in lung CD4+ T cells of neonatal mice with E. coli pneumonia [RNA-Seq]

2022-12-22 | GSE214489 | GEO

DNA methyltransferase inhibition induces dynamic gene expression changes in lung CD4+ T cells of neonatal mice with E. coli pneumonia [RRBS]

Project description:DNA methyltransferase inhibition induces dynamic gene expression changes in lung CD4+ T cells of neonatal mice with E. coli pneumonia [RRBS]

| PRJNA885515 | ENA

DNA methyltransferase inhibition induces dynamic gene expression changes in lung CD4+ T cells of neonatal mice with E. coli pneumonia [RNA-Seq]

Project description:DNA methyltransferase inhibition induces dynamic gene expression changes in lung CD4+ T cells of neonatal mice with E. coli pneumonia [RNA-Seq]

| PRJNA885514 | ENA

DNA methyltransferase inhibition induces dynamic gene expression changes in lung CD4<sup>+</sup> T cells of neonatal mice with E. coli pneumonia.

Project description:Bacterial pulmonary infections are a major cause of morbidity and mortality in neonates, with less severity in older children. Previous studies demonstrated that the DNA of CD4+ T cells in the mouse lung, whose primary responsibility is to coordinate the immune response to foreign pathogens, is differentially methylated in neonates compared with juveniles. Nevertheless, the effect of this differential DNA methylation on CD4+ T cell gene expression and response to infection remains unclear. Here we treated E. coli-infected neonatal (4-day-old) and juvenile (13-day-old) mice with decitabine (DAC), a DNA methyltransferase inhibitor with broad-spectrum DNA demethylating activity, and performed simultaneous genome-wide DNA methylation and transcriptional profiling on lung CD4+ T cells. We show that juvenile and neonatal mice experienced differential demethylation in response to DAC treatment, with larger methylation differences observed in neonates. By cross-filtering differentially expressed genes between juveniles and neonates with those sites that were demethylated in neonates, we find that interferon-responsive genes such as Ifit1 are the most down-regulated methylation-sensitive genes in neonatal mice. DAC treatment shifted neonatal lung CD4+ T cells toward a gene expression program similar to that of juveniles. Following lung infection with E. coli, lung CD4+ T cells in neonatal mice exhibit epigenetic repression of important host defense pathways, which are activated by inhibition of DNA methyltransferase activity to resemble a more mature profile.

| S-EPMC10017701 | biostudies-literature

DNA methyltransferase inhibition induces dynamic gene expression changes in lung CD4+ T cells of neonatal mice with E. coli pneumonia

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

2022-12-22 | GSE214490 | GEO

DNA methylation regulates the neonatal CD4+ T-cell response to pneumonia in mice

Project description:DNA methylation regulates the neonatal CD4+ T-cell response to pneumonia in mice

| PRJNA418111 | ENA

DNA methylation regulates the neonatal CD4+ T-cell response to pneumonia in mice

Project description:DNA methylation regulates the neonatal CD4+ T-cell response to pneumonia in mice

| PRJNA418112 | ENA

DNA methylation regulates the neonatal CD4+ T-cell response to pneumonia in mice

Project description:DNA methylation regulates the neonatal CD4+ T-cell response to pneumonia in mice

| PRJNA418097 | ENA

DNA methylation regulates the neonatal CD4+ T-cell response to pneumonia in mice

Project description:Lung CD4+ T cell responses may determine outcomes in pediatric pnuemonia. We therefore sought to define the transcriptional response and underlying DNA methyaltion landscape of lung CD4+ T cells by treating neonatal (~5 days of age) and juvenile (~15 days of age) mice with 2.8 million CFUs of E. coli or PBS (control) by aspiration. 48 hours later, lung CD4+ T cells were isolated by magnetic bead pre-enrichment and fluorescence-activated cell sorting for RNA-sequencing (RNA-seq) and modified reduced representation bisulfite sequencing (mRRBS).

2018-06-04 | GSE106806 | GEO

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