GRID-seq studies of small intestinal epithelial cells from wildtype mice
Ontology highlight
ABSTRACT: Long non-coding RNAs (lncRNAs) are critical regulators of mammalian gene programs. Metastasis Associated Lung Adenocarcinoma Transcript 1 (Malat1) is one of the most abundant lncRNA expressed in the mammalian genome. Here, we report that Malat1 regulates intestinal epithelial cell programs and contributes to tissue homeostasis and tumorigenesis. Global RNA interactions with DNA by deep sequencing (GRID-seq) experiments revealed Malat1 chromatin localization in intestinal epithelial cells from the wildtype small intestine.
Project description:Long non-coding RNAs (lncRNAs) are critical regulators of mammalian gene programs. Metastasis Associated Lung Adenocarcinoma Transcript 1 (Malat1) is the most abundant lncRNA expressed in intestinal Th17 cells critical for maintaining tissue homeostasis and regulating local inflammation. Here, we report that Malat1 negatively regulates IL-17A and IL-17F productions in intestinal Th17 cells during colitis and contributes to local inflammation. Global RNA interactions with DNA by deep sequencing (GRID-seq) coupled with transcriptomic studies revealed Malat1 is recruited to the Il17a-Il17f super enhancer in Th17 cells, and regulates Il17a-Il17f transcription.
Project description:Long non-coding RNAs (lncRNAs) are critical regulators of mammalian gene programs. Metastasis Associated Lung Adenocarcinoma Transcript 1 (Malat1) is the most abundant lncRNA expressed in intestinal Th17 cells critical for maintaining tissue homeostasis and regulating local inflammation. Here, we report that Malat1 negatively regulates IL-17A and IL-17F productions in intestinal Th17 cells during colitis and contributes to local inflammation. Global RNA interactions with DNA by deep sequencing (GRID-seq) coupled with transcriptomic studies revealed Malat1 is recruited to the Il17a-Il17f super enhancer in Th17 cells, and regulates Il17a-Il17f transcription.
Project description:The long-non-coding RNA Malat1 is abundantly expressed in all subsets of the intestinal epithelial cells (IEC). Here, we compared the transcriptome of the small intestinal and colonic epithelium of wildtype and Malat1-/- mice under steady state. We found that Malat1 is involved in IEC homeostasis, intestinal microbial balance, and regulates programs involved in intestinal cancer.
Project description:To adapt to its changing dietary environment, the digestive tract is extensively remodeled from the embryo to the adult during vertebrate development. Xenopus laevis metamorphosis is an excellent model system for studying mammalian gastrointestinal development and is used to determine the genes and signaling programs essential for intestinal development and maturation. The metamorphosing intestine can be divided into four distinct developmental time points and these were analyzed with X. laevis microarrays. Due to the high level of conservation in developmental signaling programs and homology to mammalian genes, annotations and bioinformatics analysis were based on human orthologs. Clustering of the expression patterns revealed co-expressed genes involved in essential cell processes such as apoptosis and proliferation. The two largest clusters of genes have expression peaks and troughs at the climax of metamorphosis respectively. Novel conserved gene ontology categories regulated during this period include transcriptional activity, signal transduction, and metabolic processes. Interestingly, the induced genes associated with metamorphic climax correlated with the gene expression peaks observed around birth in the mouse intestine. Thus both mouse and amphibian, share similarities at the molecular levels for intestinal maturation and remodeling, which appears to be under the influence of increasing levels of circulating thyroid hormone. Moreover, our genome-wide analysis of the intestine during development identified larval/embryo- and adult-specific genes. Detailed analysis revealed 17 larval specific genes that may represent molecular markers for human colonic cancers, while many adult specific genes are associated with dietary enzymes. This global developmental expression study provides the first detailed molecular description of intestinal remodeling and maturation during postembryonic development, which should help improve our understanding of intestinal organogenesis and human diseases. This study significantly contributes towards our understanding of the dynamics of molecular regulation during development and tissue renewal, which is important for future basic and clinical research and for medicinal applications. Time series experiment through natural metamorphosis of intestine in Xenopus laevis. Biological replicates: 3 replicates for each stage of major change during amphibian metamorphosis (except in the climax where 2 bioogical replicates were used). Universal reference design was used instead of dye-swap design for 2-color hybridizations.
Project description:To adapt to its changing dietary environment, the digestive tract is extensively remodeled from the embryo to the adult during vertebrate development. Xenopus laevis metamorphosis is an excellent model system for studying mammalian gastrointestinal development and is used to determine the genes and signaling programs essential for intestinal development and maturation. The metamorphosing intestine can be divided into four distinct developmental time points and these were analyzed with X. laevis microarrays. Due to the high level of conservation in developmental signaling programs and homology to mammalian genes, annotations and bioinformatics analysis were based on human orthologs. Clustering of the expression patterns revealed co-expressed genes involved in essential cell processes such as apoptosis and proliferation. The two largest clusters of genes have expression peaks and troughs at the climax of metamorphosis respectively. Novel conserved gene ontology categories regulated during this period include transcriptional activity, signal transduction, and metabolic processes. Interestingly, the induced genes associated with metamorphic climax correlated with the gene expression peaks observed around birth in the mouse intestine. Thus both mouse and amphibian, share similarities at the molecular levels for intestinal maturation and remodeling, which appears to be under the influence of increasing levels of circulating thyroid hormone. Moreover, our genome-wide analysis of the intestine during development identified larval/embryo- and adult-specific genes. Detailed analysis revealed 17 larval specific genes that may represent molecular markers for human colonic cancers, while many adult specific genes are associated with dietary enzymes. This global developmental expression study provides the first detailed molecular description of intestinal remodeling and maturation during postembryonic development, which should help improve our understanding of intestinal organogenesis and human diseases. This study significantly contributes towards our understanding of the dynamics of molecular regulation during development and tissue renewal, which is important for future basic and clinical research and for medicinal applications.