Chromatin signatures at transcriptional start sites separate two equally populated yet distinct classes of intergenic long noncoding RNAs
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE49460 | GEO | 2013/11/11
SECONDARY ACCESSION(S): PRJNA214036
REPOSITORIES: GEO
Similar Datasets
Project description:BACKGROUND:Mammalian transcriptomes contain thousands of long noncoding RNAs (lncRNAs). Some lncRNAs originate from intragenic enhancers which, when active, behave as alternative promoters producing transcripts that are processed using the canonical signals of their host gene. We have followed up this observation by analyzing intergenic lncRNAs to determine the extent to which they might also originate from intergenic enhancers. RESULTS:We integrated high-resolution maps of transcriptional initiation and transcription to annotate a conservative set of intergenic lncRNAs expressed in mouse erythroblasts. We subclassified intergenic lncRNAs according to chromatin status at transcriptional initiation regions, defined by relative levels of histone H3K4 mono- and trimethylation. These transcripts are almost evenly divided between those arising from enhancer-associated (elncRNA) or promoter-associated (plncRNA) elements. These two classes of 5' capped and polyadenylated RNA transcripts are indistinguishable with regard to their length, number of exons or transcriptional orientation relative to their closest neighboring gene. Nevertheless, elncRNAs are more tissue-restricted, less highly expressed and less well conserved during evolution. Of considerable interest, we found that expression of elncRNAs, but not plncRNAs, is associated with enhanced expression of neighboring protein-coding genes during erythropoiesis. CONCLUSIONS:We have determined globally the sites of initiation of intergenic lncRNAs in erythroid cells, allowing us to distinguish two similarly abundant classes of transcripts. Different correlations between the levels of elncRNAs, plncRNAs and expression of neighboring genes suggest that functional lncRNAs from the two classes may play contrasting roles in regulating the transcript abundance of local or distal loci.
| S-EPMC4054604 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-11-11 | E-GEOD-49460 | biostudies-arrayexpress
Project description:Chromatin signatures at transcriptional start sites separate two equally populated yet distinct classes of intergenic long noncoding RNAs
| PRJNA214036 | ENA
Project description:Long intergenic noncoding RNAs (lincRNAs) are one of the major unexplored components of genomes. Here we re-analyzed a published methylated DNA immunoprecipitation sequencing (MeDIP-seq) dataset to characterize the DNA methylation pattern of pig lincRNA genes in adipose and muscle tissues. Our study showed that the methylation level of lincRNA genes was higher than that of mRNA genes, with similar trends observed in comparisons of the promoter, exon or intron regions. Different methylation pattern were observed across the transcription start sites (TSS) of lincRNA and protein-coding genes. Furthermore, an overlap was observed between many lincRNA genes and differentially methylated regions (DMRs) identified among different breeds of pigs, which show different fat contents, sexes and anatomic locations of tissues. We identify a lincRNA gene, linc-sscg3623, that displayed differential methylation levels in backfat between Min and Large White pigs at 60 and 120 days of age. We found that a demethylation process occurred between days 150 and 180 in the Min and Large White pigs, which was followed by remethylation between days 180 and 210. These results contribute to our understanding of the domestication of domestic animals and identify lincRNA genes involved in adipogenesis and muscle development.
| S-EPMC4616017 | biostudies-literature
Project description:Long intergenic noncoding RNAs (lincRNAs) play a crucial role in many biological processes. The rat is an important model organism in biomedical research. Recent studies have detected rat lincRNA genes from several samples. However, identification of rat lincRNAs using large-scale RNA-seq datasets remains unreported. Herein, using more than 100 billion RNA-seq reads from 59 publications together with RefSeq and UniGene annotated RNAs, we report 39,154 lincRNA transcripts encoded by 19,162 lincRNA genes in the rat. We reveal sequence and expression similarities in lincRNAs of rat, mouse and human. DNA methylation level of lincRNAs is higher than that of protein-coding genes across the transcription start sites (TSSs). And, three lincRNA genes overlap with differential methylation regions (DMRs) which associate with spontaneously hypertensive disease. In addition, there are similar binding trends for three transcription factors (HNF4A, CEBPA and FOXA1) between lincRNA genes and protein-coding genes, indicating that they harbour similar transcription regulatory mechanisms. To date, this is the most comprehensive assessment of lincRNAs in the rat genome. We provide valuable data that will advance lincRNA research using rat as a model.
| S-EPMC5665958 | biostudies-literature
Project description:BackgroundOver 10,000 long intergenic non-coding RNAs (lincRNAs) have been identified in the human genome. Some have been well characterized and known to participate in various stages of gene regulation. In the post-transcriptional process, another class of well-known small non-coding RNA, or microRNA (miRNA), is very active in inhibiting mRNA. Though similar features between mRNA and lincRNA have been revealed in several recent studies, and a few isolated miRNA-lincRNA relationships have been observed. Despite these advances, the comprehensive miRNA regulation pattern of lincRNA has not been clarified.MethodsIn this study, we investigated the possible interaction between the two classes of non-coding RNAs. Instead of using the existing long non-coding database, we employed an ab initio method to annotate lincRNAs expressed in a group of normal breast tissues and breast tumors.ResultsApproximately 90 lincRNAs show strong reverse expression correlation with miRNAs, which have at least one predicted target site presented. These target sites are statistically more conserved than their neighboring genetic regions and other predicted target sites. Several miRNAs that target to these lincRNAs are known to play an essential role in breast cancer.ConclusionSimilar to inhibiting mRNAs, miRNAs show potential in promoting the degeneration of lincRNAs. Breast-cancer-related miRNAs may influence their target lincRNAs resulting in differential expression in normal and malignant breast tissues. This implies the miRNA regulation of lincRNAs may be involved in the regulatory process in tumor cells.
| S-EPMC3552696 | biostudies-literature
Project description:ObjectiveTranscriptome profiling of human tissues has revealed thousands of long intergenic noncoding RNAs (lincRNAs) at loci identified through large-scale genome-wide studies for complex cardiometabolic traits. This raises the question of whether genetic variation at nonconserved lincRNAs has any systematic association with complex disease, and if so, how different this pattern is from conserved lincRNAs. We evaluated whether the associations between nonconserved lincRNAs and 8 complex cardiometabolic traits resemble or differ from the pattern of association for conserved lincRNAs. Approach and Results: Our investigation of over 7000 lincRNA annotations from GENCODE Release 33-GRCh38.p13 for complex trait genetic associations leveraged several large, established meta-analyses genome-wide association study summary data resources, including GIANT (Genetic Investigation of Anthropometric Traits), UK Biobank, GLGC (Global Lipids Genetics Consortium), Cardiogram (Coronary Artery Disease Genome Wide Replication and Meta-Analysis), and DIAGRAM (Diabetes Genetics Replication and Meta-Analysis)/DIAMANTE (Diabetes Meta-Analysis of Trans-Ethnic Association Studies). These analyses revealed that (1) nonconserved lincRNAs associate with a range of cardiometabolic traits at a rate that is generally consistent with conserved lincRNAs; (2) these findings persist across different definitions of conservation; and (3) overall across all cardiometabolic traits, approximately one-third of genome-wide association study-associated lincRNAs are nonconserved, and this increases to about two-thirds using a more stringent definition of conservation.ConclusionsThese findings suggest that the traditional notion of conservation driving prioritization for functional and translational follow-up of complex cardiometabolic genomic discoveries may need to be revised in the context of the abundance of nonconserved long noncoding RNAs in the human genome and their apparent predilection to associate with complex cardiometabolic traits.
| S-EPMC7886007 | biostudies-literature
Project description:Long noncoding RNAs (lncRNAs) have emerged as important regulators of many biological processes, including embryogenesis and development. To provide a systematic analysis of lncRNAs expressed during chicken embryogenesis, we used Iso-Seq and RNA-Seq to identify potential lncRNAs at embryonic stages from d 1 to d 8 of incubation: sequential stages covering gastrulation, somitogenesis, and organogenesis. The data characterized an expanded landscape of lncRNAs, yielding 45,410 distinct lncRNAs (31,282 genes). Amongst these, a set of 13,141 filtered intergenic lncRNAs (lincRNAs) transcribed from 9803 lincRNA gene loci, of which, 66.5% were novel, were further analyzed. These lincRNAs were found to share many characteristics with mammalian lincRNAs, including relatively short lengths, fewer exons, lower expression levels, and stage-specific expression patterns. Functional studies motivated by "guilt-by-association" associated individual lincRNAs with specific GO functions, providing an important resource for future studies of lincRNA function. Most importantly, a weighted gene co-expression network analysis suggested that genes of the brown module were specifically associated with the day 2 stage. LincRNAs within this module were co-expressed with proteins involved in hematopoiesis and lipid metabolism. This study presents the systematic identification of lincRNAs in developing chicken embryos and will serve as a powerful resource for the study of lincRNA functions.
| S-EPMC8170422 | biostudies-literature
Project description:Long intergenic noncoding RNAs (lincRNAs) have been suggested as playing important roles in human gene regulation. The majority of annotated human lincRNAs include multiple exons and are alternatively spliced. However, the connections between alternative RNA splicing (AS) and the functions/regulations of lincRNAs have remained elusive. In this study, we compared the sequence evolution and biological features between single-exonic lincRNAs and multi-exonic lincRNAs (SELs and MELs, respectively) that were present only in the hominoids (hominoid-specific) or conserved in primates (primate-conserved). The MEL exons were further classified into alternatively spliced exons (ASEs) and constitutively spliced exons (CSEs) for evolutionary analyses. Our results indicate that SELs and MELs differed significantly from each other. Firstly, in hominoid-specific lincRNAs, MELs (both CSEs and ASEs) evolved slightly more rapidly than SELs, which evolved approximately at the neutral rate. In primate-conserved lincRNAs, SELs and ASEs evolved slightly more slowly than CSEs and neutral sequences. The evolutionary path of hominid-specific lincRNAs thus seemed to have diverged from that of their more ancestral counterparts. Secondly, both of the exons and transcripts of SELs were significantly longer than those of MELs, and this was probably because SEL transcripts were more resistant to RNA splicing than MELs. Thirdly, SELs were physically closer to coding genes than MELs. Fourthly, SELs were more widely expressed in human tissues than MELs. These results suggested that SELs and MELs represented two biologically distinct groups of genes. In addition, the SEL-MEL and ASE-CSE differences implied that splicing might be important for the functionality or regulations of lincRNAs in primates.
| S-EPMC4264600 | biostudies-literature
Project description:Long intergenic noncoding RNAs (lincRNAs) are increasingly recognized as potential key regulators of heart development and related diseases, but their identities and functions remain elusive. In this study, we sought to identify and characterize the cardiac lincRNA transcriptome in the experimentally accessible zebrafish model by integrating bioinformatics analysis with experimental validation. By conducting genome-wide RNA sequencing profiling of zebrafish embryonic hearts, adult hearts, and adult muscle, we generated a high-confidence set of 813 cardiac lincRNA transcripts, 423 of which are novel. Among these lincRNAs, 564 are expressed in the embryonic heart, and 730 are expressed in the adult heart, including 2 novel lincRNAs, TCONS_00000891 and TCONS_00028686, which exhibit cardiac-enriched expression patterns in adult heart. Using a method similar to a fetal gene program, we identified 51 lincRNAs with differential expression patterns between embryonic and adult hearts, among which TCONS_00009015 responded to doxorubicin-induced cardiac stress. In summary, our genome-wide systematic identification and characterization of cardiac lincRNAs lays the foundation for future studies in this vertebrate model to elucidate crucial roles for cardiac lincRNAs during heart development and cardiac diseases.
| S-EPMC5430783 | biostudies-literature