Browse
Submit Data
Databases
API
Help

Dataset Information

31 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Epigenetic modifications and long noncoding RNAs influence pancreas development and function.

ABSTRACT: Insulin-producing ? cells within the pancreatic islet of Langerhans are responsible for maintaining glucose homeostasis; the loss or malfunction of ? cells results in diabetes mellitus. Recent advances in cell purification strategies and sequencing technologies as well as novel molecular tools have revealed that epigenetic modifications and long noncoding RNAs (lncRNAs) represent an integral part of the transcriptional mechanisms regulating pancreas development and ? cell function. Importantly, these findings have uncovered a new layer of gene regulation in the pancreas that can be exploited to enhance the restoration and/or repair of ? cells to treat diabetes.

SUBMITTER: Arnes L

PROVIDER: S-EPMC4458180 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Epigenetic modifications and long noncoding RNAs influence pancreas development and function.

Arnes Luis L Sussel Lori L

Trends in genetics : TIG 20150323 6

Insulin-producing β cells within the pancreatic islet of Langerhans are responsible for maintaining glucose homeostasis; the loss or malfunction of β cells results in diabetes mellitus. Recent advances in cell purification strategies and sequencing technologies as well as novel molecular tools have revealed that epigenetic modifications and long noncoding RNAs (lncRNAs) represent an integral part of the transcriptional mechanisms regulating pancreas development and β cell function. Importantly, ...[more]

PMID: 25812926

Similar Datasets

Epigenetic modifications in pancreas development, diabetes, and therapeutics.

Project description:A recent International Diabetes Federation report suggests that more than 463 million people between 20 and 79 years have diabetes. Of the 20 million women affected by hyperglycemia during pregnancy, 84% have gestational diabetes. In addition, more than 1.1 million children or adolescents are affected by type 1 diabetes. Factors contributing to the increase in diabetes prevalence are complex and include contributions from genetic, environmental, and epigenetic factors. However, molecular regulatory mechanisms influencing the progression of an individual towards increased susceptibility to metabolic diseases such as diabetes are not fully understood. Recent studies suggest that the pathogenesis of diabetes involves epigenetic changes, resulting in a persistently dysregulated metabolic phenotype. This review summarizes the role of epigenetic mechanisms, mainly DNA methylation and histone modifications, in the development of the pancreas, their contribution to the development of diabetes, and the potential employment of epigenetic modulators in diabetes treatment.

| S-EPMC9306699 | biostudies-literature

The role of long noncoding RNAs during pancreas development

Project description:LncRNAs are developmentally regulated and highly cell type-specific non-coding RNAs that have emerged as important regulators of cell fate commitment and maintenance. In this study, we dissected the role of lncRNAs in human pancreas development by classifying lncRNAs based on their dynamic regulation, subcellular localization, and engagement with ribosomes during the stepwise differentiation of human embryonic stem cells (hESCs) towards pancreatic fate. We then deleted 10 candidate lncRNAs in hESCs and characterized the knockout phenotypes of pancreatic developmental intermediates, prioritizing dynamically regulated lncRNAs with validated translation potential and proximity to developmental TFs. This small-scale loss-of-function screen revealed that most lncRNAs are dispensable for pancreatic development and the regulation of nearby genes. We identify LINC00261 as the first translated lncRNA involved in human endocrine cell development, and show that it regulates gene expression in pancreatic progenitor cells in trans rather than cis. Through systematic dissection of LINC00261's coding and noncoding functions, we can exclude a role for the produced micropeptides in this process. Instead, we posit that, over the course of pancreatic differentiation, the biological activity of multiple lncRNAs is controlled by a regulatory, translation machinery dependent mechanism that employs ribosome engagement and short open reading frame translation to dose lncRNA activity in the nucleus. It is conceivable that inadequate nuclear LINC00261 dosage during human pancreas development could predispose individuals to developing diabetes.

2020-08-03 | GSE144682 | GEO

Gene activation-associated long noncoding RNAs function in mouse preimplantation development.

Project description:In mice, zygotic activation occurs for a wide variety of genes, mainly at the 2-cell stage. Long noncoding RNAs (lncRNAs) are increasingly being recognized as modulators of gene expression. In this study, directional RNA-seq of MII oocytes and 2-cell embryos identified more than 1000 divergently transcribed lncRNA/mRNA gene pairs. Expression of these bidirectional promoter-associated noncoding RNAs (pancRNAs) was strongly associated with the upregulation of their cognate genes. Conversely, knockdown of three abundant pancRNAs led to reduced mRNA expression, accompanied by sustained DNA methylation even in the presence of enzymes responsible for DNA demethylation. In particular, microinjection of siRNA against the abundant pancRNA partner of interleukin 17d (Il17d) mRNA at the 1-cell stage caused embryonic lethality, which was rescued by supplying IL17D protein in vitro at the 4-cell stage. Thus, this novel class of lncRNAs can modulate the transcription machinery in cis to activate zygotic genes and is important for preimplantation development.

| S-EPMC4352986 | biostudies-literature

The role of long noncoding RNAs during pancreas development

Project description:The role of long noncoding RNAs during pancreas development

| PRJNA604580 | ENA

Long noncoding RNAs: Central to nervous system development.

Project description:The development of the central nervous system (CNS) is a complex orchestration of stem cells, transcription factors, growth/differentiation factors, and epigenetic control. Noncoding RNAs have been identified, classified, and studied for their functional roles in many systems including the CNS. In particular, the class of long noncoding RNAs (lncRNAs) has generated both enthusiasm and skepticism due to the unexpected discovery, the diversity of mechanisms, and the lower level of expression than found in protein-coding RNAs. Here we describe evidence supporting the role of lncRNAs in driving CNS-specific differentiation. It is clear that lncRNAs exhibit a functional diversity that makes their study and compartmentalization more challenging than other classes of noncoding RNAs. We predict, however, that lncRNAs will be essential for the characterization of discrete neuronal cell types in the age of single-cell transcriptomics and that these regulatory RNAs contribute to the multitude of functional mechanisms during CNS differentiation that will rival the diversities of protein-based mechanisms.

| S-EPMC5148644 | biostudies-literature

Pan-cancer transcriptome analysis reveals long noncoding RNAs with conserved function.

Project description:A growing number of gene-centric studies have highlighted the emerging significance of lncRNAs in cancer. However, these studies primarily focus on a single cancer type. Therefore, we conducted a pan-cancer analysis of lncRNAs comparing tumor and matched normal expression levels using RNA-Seq data from ? 3,000 patients in 8 solid tumor types. While the majority of differentially expressed lncRNAs display tissue-specific expression we discovered 229 lncRNAs with outlier or differential expression across multiple cancers, which we refer to as 'onco-lncRNAs'. Due to their consistent altered expression, we hypothesize that these onco-lncRNAs may have conserved oncogenic and tumor suppressive functions across cancers. To address this, we associated the onco-lncRNAs in biological processes based on their co-expressed protein coding genes. To validate our predictions, we experimentally confirmed cell growth dependence of 2 novel oncogenic lncRNAs, onco-lncRNA-3 and onco-lncRNA-12, and a previously identified lncRNA CCAT1. Overall, we discovered lncRNAs that may have broad oncogenic and tumor suppressor roles that could significantly advance our understanding of cancer lncRNA biology.

| S-EPMC4615893 | biostudies-other

Long noncoding RNAs in B-cell development and activation.

Project description:Long noncoding RNAs (lncRNAs) are potentially important regulators of cell differentiation and development, but little is known about their roles in B lymphocytes. Using RNA-seq and de novo transcript assembly, we identified 4516 lncRNAs expressed in 11 stages of B-cell development and activation. Most of these lncRNAs have not been previously detected, even in the closely related T-cell lineage. Comparison with lncRNAs previously described in human B cells identified 185 mouse lncRNAs that have human orthologs. Using chromatin immunoprecipitation-seq, we classified 20% of the lncRNAs as either enhancer-associated (eRNA) or promoter-associated RNAs. We identified 126 eRNAs whose expression closely correlated with the nearest coding gene, thereby indicating the likely location of numerous enhancers active in the B-cell lineage. Furthermore, using this catalog of newly discovered lncRNAs, we show that PAX5, a transcription factor required to specify the B-cell lineage, bound to and regulated the expression of 109 lncRNAs in pro-B and mature B cells and 184 lncRNAs in acute lymphoblastic leukemia.

| S-EPMC5000579 | biostudies-literature

Epigenetic coordination of embryonic heart transcription by dynamically regulated long noncoding RNAs.

Project description:The vast majority of mammalian DNA does not encode for proteins but instead is transcribed into noncoding (nc)RNAs having diverse regulatory functions. The poorly characterized subclass of long ncRNAs (lncRNAs) can epigenetically regulate protein-coding genes by interacting locally in cis or distally in trans. A few reports have implicated specific lncRNAs in cardiac development or failure, but precise details of lncRNAs expressed in hearts and how their expression may be altered during embryonic heart development or by adult heart disease is unknown. Using comprehensive quantitative RNA sequencing data from mouse hearts, livers, and skin cells, we identified 321 lncRNAs present in the heart, 117 of which exhibit a cardiac-enriched pattern of expression. By comparing lncRNA profiles of normal embryonic (∼E14), normal adult, and hypertrophied adult hearts, we defined a distinct fetal lncRNA abundance signature that includes 157 lncRNAs differentially expressed compared with adults (fold-change ≥ 50%, false discovery rate = 0.02) and that was only poorly recapitulated in hypertrophied hearts (17 differentially expressed lncRNAs; 13 of these observed in embryonic hearts). Analysis of protein-coding mRNAs from the same samples identified 22 concordantly and 11 reciprocally regulated mRNAs within 10 kb of dynamically expressed lncRNAs, and reciprocal relationships of lncRNA and mRNA levels were validated for the Mccc1 and Relb genes using in vitro lncRNA knockdown in C2C12 cells. Network analysis suggested a central role for lncRNAs in modulating NFκB- and CREB1-regulated genes during embryonic heart growth and identified multiple mRNAs within these pathways that are also regulated, but independently of lncRNAs.

| S-EPMC4143054 | biostudies-literature

Decoding Noncoding RNAs: Role of MicroRNAs and Long Noncoding RNAs in Ocular Neovascularization.

Project description:Ocular neovascularization is a pathological sequel of multiple eye diseases. Based on the anatomical site into which the abnormal neovessels grow, ocular neovascularization can be categorized into corneal neovascularization, choroidal neovascularization, and retinal neovascularization. Each category is intractable, and may lead to blindness if not appropriately treated. However, the current therapeutic modalities, including laser photocoagulation, vitrectomy surgery, and anti-VEGF drugs, raise concerns due to limited efficacy, damage on retinal parenchyma and vasculature, and the patients' unresponsiveness to the treatments. Therefore, the in-depth study on pathogenesis of and the search for novel therapeutic targets to the ocular neovascularization are needed. During the last 10 years or so, a large number of literatures have emerged indicating a critical role of noncoding RNAs, particularly microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), in the pathogenesis and regulation of the ocular neovascularization. This review summarizes the current understanding of the biosynthesis and functions of the miRNAs and lncRNAs, the regulation of the miRNAs and lncRNAs in neovascular eye diseases, as well as the roles of these noncoding RNAs in the disease models of ocular neovascularization, in the hope that it could provide clues for the pathogenesis of and molecular targets to the ocular neovascularization.

| S-EPMC5566112 | biostudies-other

Long noncoding RNAs with enhancer-like function in human cells.

Project description:While the long noncoding RNAs (ncRNAs) constitute a large portion of the mammalian transcriptome, their biological functions has remained elusive. A few long ncRNAs that have been studied in any detail silence gene expression in processes such as X-inactivation and imprinting. We used a GENCODE annotation of the human genome to characterize over a thousand long ncRNAs that are expressed in multiple cell lines. Unexpectedly, we found an enhancer-like function for a set of these long ncRNAs in human cell lines. Depletion of a number of ncRNAs led to decreased expression of their neighboring protein-coding genes, including the master regulator of hematopoiesis, SCL (also called TAL1), Snai1 and Snai2. Using heterologous transcription assays we demonstrated a requirement for the ncRNAs in activation of gene expression. These results reveal an unanticipated role for a class of long ncRNAs in activation of critical regulators of development and differentiation.

| S-EPMC4108080 | biostudies-literature

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