Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genes controlling the activation of natural killer lymphocytes are epigenetically remodeled in intestinal cells from germ-free mice

ABSTRACT: Remodeling of the gut microbiota is implicated in various metabolic and inflammatory diseases of the gastrointestinal tract. We hypothesized that the gut microbiota affects the DNA methylation profile of intestinal epithelial cells (IECs) which could, in turn, alter intestinal function. Here, we used mass spectrometry and methylated DNA capture to respectively investigate global and genome-wide DNA methylation of intestinal epithelial cells from germ-free (GF) and conventionally raised mice (CONV-R). In colonic IECs from GF mice, DNA was markedly hypermethylated. This was associated with a dramatic loss of Ten-Eleven-Translocation activity, a lower DNA methyltransferase activity and lower circulating levels of the one carbon metabolites cobalamin and folate. At the gene level, we found an enrichment for differentially methylated regions at proximity of genes regulating cytotoxicity of Natural Killer cells (FDR < 8.9E-6), notably members of the natural killer group 2 member D ligand superfamily Raet. Our results suggest that altered activity of methylation-modifying enzymes in GF mice influences the IEC epigenome at genes involved in the crosstalk between intestinal and immune cells. Epigenetic reprogramming of IECs by the gut microbiota may modulate intestinal function in diseases associated with altered gut microbiota.

ORGANISM(S): Mus musculus

PROVIDER: GSE117434 | GEO | 2019/01/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Microbiota modulate transcription in the intestinal epithelium without remodeling the accessible chromatin landscape

Project description:We profiled transcriptome and accessible chromatin landscapes in intestinal epithelial cells (IECs) from mice reared in the presence or absence of microbiota. We show that regional differences in gene transcription along the intestinal tract were accompanied by major alterations in chromatin organization. Surprisingly, we discovered that microbiota modify host gene transcription in IECs without significantly impacting the accessible chromatin landscape. Instead, microbiota regulation of host gene transcription might be achieved by differential expression of specific TFs and enrichment of their binding sites in nucleosome depleted CRRs near target genes. Our results suggest that the chromatin landscape in IECs is pre-programmed by the host in a region-specific manner to permit responses to microbiota through binding of open CRRs by specific TFs. mRNA and accessible chromatin (DNase-seq) profiles from colonic and ileal IECs were compared between conventionally-raised (CR), germ-free (GF), and conventionalized (CV) C57BL/6 mice.

2014-06-07 | E-GEOD-57919 | biostudies-arrayexpress

The intestinal microbiota programs DNA methylation to control tissue homeostasis and inflammation [RNA-seq]

Project description:Although much research has been done on the diversity of gut microbiome, little is known about the way it influences intestinal homeostasis under normal and pathogenic conditions. Epigenetic mechanisms have recently been suggested as operating at the interface between the microbiota and the intestinal epithelium cells (IECs). Using genome-wide analyses, we discovered that exposure to microbiota induced both global DNA hypomethylation and localized changes at regulatory elements, which culminates in activation of a set of “early sentinel” response genes that play a role in maintaining gut homeostasis. Furthermore, we demonstrated that exposure to microbiota in acute inflammation results in profound DNA methylation and chromatin accessibility changes at regulatory elements leading to alterations in the gene expression program in colitis and colon cancer. Our studies add a new dimension to our understanding of the cross talk between the microbiota and IECs, and provide the foundation for how microbiota impact epigenetic programming.

2020-02-06 | GSE136840 | GEO

The intestinal microbiota programs DNA methylation to control tissue homeostasis and inflammation [BiSulfite-seq]

2020-02-06 | GSE125978 | GEO

The intestinal microbiota programs DNA methylation to control tissue homeostasis and inflammation [ATAC-Seq]

2020-02-06 | GSE141458 | GEO

Transcriptional Modulation of Genes by Gut Microbiota in Germfree and Conventional Mice

Project description:To characterize the effect of microbiota on global gene expression in the distal small intestine during postnatal gut development we employed mouse models with experimental colonization by intestinal microbiota. Using microarray analysis to assess global gene expression in ileal mucosa at the critical stage of intestinal development /maturation associated with weaning, and asking how expression is affected by microbial colonization In the study presented here, preweaned and postweaned GF, SPF mouse small intestinal total RNAs were used. Also, 3-week-old gnotobiotic mouse as well as GF mouse small intestinal RNAs were used.

2013-03-02 | E-GEOD-44788 | biostudies-arrayexpress

Microbiota regulate intestinal epithelial gene expression by suppressing the transcription factor Hepatocyte nuclear factor 4 alpha (Mouse ChIP-seq, RNA-seq, and DNase-seq)

Project description:We profiled transcriptome and chromatin landscapes in jejunal mouse intestinal epithelial cells (IECs) from mice reared in the absence (Germ Free or GF) or presence (Conventionalized or CV) of microbiota. We show that microbiota colonization results in changes in histone modifications at hundreds of enhancers that are associated with microbiota-regulated genes. Furthermore, we show that microbiota colonization is associated with a drastic genome-wide reduction in Hnf4a and Hnf4g binding.

2017-03-27 | GSE90461 | GEO

Adaptor molecule of DNA methylation in IECs

Project description:We previously reported that gut microbiota induce de novo DNA methylation of the TLR4 gene in intestinal epithelial cells. Since DNA methyltransferase (DNMT) 3 mediates the transfer of methyl groups to any gene undergoing de novo methylation, the question of how gut microbiota induce the recruitment of DNMT3 to specific genes, including TLR4, remains to be addressed. In this study, we tried to identify an adaptor molecule that recruits DNMT3b to the TLR4 gene by comparing expression of DNMT3-interacting proteins between IEC lines with hypermethylated and hypomethylated TLR4 gene.

2023-03-11 | PXD035777 | Pride

RNA-seq of WT ileum with DEX, Zn and untreated controls

Project description:The cytokine TNF drives inflammatory diseases, e.g. Crohn disease. In a mouse model of TNF-induced systemic inflammatory response syndrome (SIRS), severe impact on intestinal epithelial cells (IECs) is observed. Zinc confers complete protection in this model. We found that zinc no longer protects in animals which lack glucocorticoids (GCs), or express mutant versions of their receptor GR in IECs, nor in mice which lack gut microbiota. RNA-seq studies in IECs showed that zinc caused reduction of expression of constitutive (STAT1-induced) interferon-stimulated response (ISRE) genes and Interferon Regulatory Factor (IRF) genes. Since some of these genes are involved in TNF-induced cell death in intestinal crypt Paneth cells, and since zinc has direct effects on the composition of the gut microbiota (such as several Staphylococcus species) and on TNF-induced Paneth cell death, we postulate a new zinc-related anti-inflammatory mechanism. Zinc modulates the gut microbiota, causing less induction of ISRE/IRF genes in crypt cells, less TNF-induced necroptosis in Paneth cells and less fatal evasion of gut bacteria into the system.

2020-09-07 | GSE156119 | GEO

RNA-seq of GR WT and GR DIM ileum/IEC with DEX, Zn and untreated controls

2020-09-07 | GSE156242 | GEO

RNA-seq of WT liver with DEX, Zn and untreated controls

2020-08-15 | GSE156282 | GEO