Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE141458 | GEO | 2020/02/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The intestinal microbiota programs DNA methylation to control tissue homeostasis and inflammation [BiSulfite-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 | GSE125978 | GEO

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

2020-02-06 | GSE136840 | GEO

In vivo loss of TET2 and TET2 results in aberrant differentiation and homeostasis in the small intestine

Project description:Although much research has been done on the diversity of the gut microbiome, little is known about how it influences intestinal homeostasis under normal and pathogenic conditions. Epigenetic mechanisms have recently been suggested to operate at the interface between the microbiota and the intestinal epithelium. We performed whole-genome bisulfite sequencing on conventionally raised and germ-free mice, and discovered that exposure to commensal microbiota induced localized DNA methylation changes at regulatory elements, which are TET2/3-dependent. This culminated in the activation of a set of ‘early sentinel’ response genes to maintain intestinal homeostasis. Furthermore, we demonstrated that exposure to the microbiota in dextran sodium sulfate-induced acute inflammation results in profound DNA methylation and chromatin accessibility changes at regulatory elements, leading to alterations in gene expression programs enriched in colitis- and colon-cancer-associated functions. Finally, by employing genetic interventions, we show that microbiota-induced epigenetic programming is necessary for proper intestinal homeostasis in vivo.

2022-06-16 | GSE206169 | GEO

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

Project description: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.

2019-01-23 | GSE117434 | GEO

Mouse intestinal epithelial cells in the deficiency of Foxo1

Project description:Mucus produced by goblet cells in the gastrointestinal (GI) tract forms a biological barrier that protects the intestine from invasion by commensals and pathogens. However, the host-derived regulatory network that controls mucus secretion and thereby changing gut microbiota has not been well studied. We found Forkhead box protein O1 (Foxo1) regulates mucus secretion by goblet cells and determines intestinal homeostasis. Loss of Foxo1 in intestinal epithelial cells (IECs) results in a defect in goblet cell autophagy and mucus secretion, leading to impaired gut microenvironment and dysbiosis.

2021-06-23 | GSE178650 | GEO

miR-181 regulates colonic inflammation

Project description:The intestinal epithelium is a key physical interface that integrates dietary and microbial signals to regulate nutrient uptake and mucosal homeostasis. Intestinal epithelial cells (IECs) have a high turnover rate driven by the death of terminally differentiated cells with concurrent stem cell proliferation, a process critical for maintaining intestinal homeostasis and protecting against mucosal inflammation. The transcriptional programs that regulate IEC quiescence, proliferation, and differentiation have been well-characterized. However, how gene expression networks critical for IEC functions are regulated at the post-transcriptional level during homeostasis or inflammatory disease remains poorly understood. Herein, we show that a conserved family of microRNAs, miR-181, is significantly downregulated in IECs from patients with inflammatory bowel disease and mice with chemical-induced colitis. Strikingly, we showed that miR-181 expression within IECs, but not the hematopoietic system, is required for protection against the development of severe colonic inflammation in response to epithelial injury in mice. Mechanistically, we showed that miR-181 expression increases the proliferative capacity of IECs, likely through the regulation of Wnt signaling, independently of gut microbiota composition. As epithelial reconstitution is crucial for restoring intestinal homeostasis after injury, the miR-181 family represents a potential novel therapeutic target in IECs for protection against severe intestinal inflammation.

2022-07-25 | GSE208410 | GEO

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 WT liver with DEX, Zn and untreated controls

2020-08-15 | GSE156282 | GEO

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

2020-09-07 | GSE156242 | GEO

IkappaBzeta Controls IL-17-triggered Gene Expression Program in Intestinal Epithelial Cells that Prevents Expansion of SFB and Attenuates Autoimmune Disorders [ATAC-Seq]

Project description:Control of gut microbes is crucial for not only local defense in the intestine but also proper systemic immune responses. Although intestinal epithelial cells (IECs) play important roles in cytokine-mediated control of enterobacteria, the underlying mechanisms are not fully understood. Here we show that deletion of IkappaBzeta in IECs in mice leads to dysbiosis with marked expansion of segmented filamentous bacteria (SFB), thereby enhancing Th17 cell development and exacerbating autoimmune inflammatory diseases. Mechanistically, the IkappaBzeta deficiency results in Paneth cell loss and impaired expression of IL-17-inducible genes involved in IgA production. The Paneth cell loss is caused by aberrant activation of IFN-gamma signaling and a failure of IL-17-mediated recovery from IFN-gamma-induced damage. Thus, the IL-17R–IkappaBzeta axis in IECs contributes to the maintenance of intestinal homeostasis by serving as a key component in a regulatory loop consisting of the gut microbiota and immune cells

2022-12-07 | GSE188253 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data