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

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

PROVIDER: PRJNA849530 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19662892_1.fastq.gz	Fastqsanger.gz
	SRR19662892_2.fastq.gz	Fastqsanger.gz
	SRR19662893_1.fastq.gz	Fastqsanger.gz
	SRR19662893_2.fastq.gz	Fastqsanger.gz
	SRR19662894_1.fastq.gz	Fastqsanger.gz

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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

TET2 and TET3 loss disrupts small intestine differentiation and homeostasis

Project description:TET2 and TET3 loss disrupts small intestine differentiation and homeostasis

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TET2 and TET3 loss disrupts small intestine differentiation and homeostasis [Bisulfite-seq]

Project description:The Ten-eleven translocation (TET) DNA demethylases play a well-known role in epigenetic regulation and mouse development. However, their function in cellular differentiation and tissue homeostasis remains poorly understood . Since previous results have implied Tet2/3 in mouse intestinal inflammation, we ablated both enzymes in intestinal epithelial cells (IECs). Our results show that the corresponding mice developed a novel phenotype displaying a severe homeostasis imbalance and a blockage in differentiation trajectories. Transcriptomic, single-cell RNA sequencing (scRNA-seq), single-molecule fluorescence in situ hybridization (sm-FISH), and immunohistochemical analyses revealed that the Tet2/3-deleted mice show a massive loss of mature Paneth cells concomitant with fewer Tuft and more enteroendocrine cells. Further results showed major changes in DNA methylation at putative enhancers, which were associated with cell fate-determining transcription factors and functional effector genes. Notably, pharmacological inhibition of DNA methylation partially rescued the methylation and cellular phenotypes. Moreover, the loss of Tet2/3 results in an altered microbiome, presumably increasing gut susceptibility to inflammatory signals (Ansari et al., 2020). Together, our results uncovered previously unrecognized critical roles for DNA demethylation in intestinal development and function, culminating in the establishment of normal intestinal crypts in mice.

2023-05-22 | GSE200227 | GEO

TET2 and TET3 loss disrupts small intestine differentiation and homeostasis [scRNA-seq]

2023-05-22 | GSE200229 | GEO

TET2 and TET3 loss disrupts small intestine differentiation and homeostasis [RNA-seq]

2023-05-22 | GSE200228 | GEO

TET2 and TET3 loss disrupts small intestine differentiation and homeostasis [scRNA-seq]

Project description:TET2 and TET3 loss disrupts small intestine differentiation and homeostasis [scRNA-seq]

| PRJNA823709 | ENA

TET2 and TET3 loss disrupts small intestine differentiation and homeostasis [RNA-seq]

Project description:TET2 and TET3 loss disrupts small intestine differentiation and homeostasis [RNA-seq]

| PRJNA823710 | ENA

TET2 and TET3 loss disrupts small intestine differentiation and homeostasis [Bisulfite-seq]

Project description:TET2 and TET3 loss disrupts small intestine differentiation and homeostasis [Bisulfite-seq]

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OGT, H2B S112GlcNAc, TET2 ChIP-seq results

Project description:TET2 directly interacts with OGT, which is important for the chromatin association of OGT in vivo. Although this specific interaction does not regulate the enzymatic activity of TET2, it facilitates OGT-dependent histone O-GlcNAcylation. Moreover, OGT associates with TET2 at transcription starting sites (TSS). Down-regulation of TET2 reduces the amount of H2B S112 GlcNAc marks in vivo, which are associated with gene transcription regulation. We found that OGT interacts with TET2 tightly. Using ChIP-seq with specific antibodies, we tested the co-localization of TET2 and OGT in genome level.

2012-12-11 | E-GEOD-41720 | biostudies-arrayexpress

OGT, H2B S112GlcNAc, TET2 ChIP-seq results

2012-12-11 | GSE41720 | GEO