Long non-coding RNAs have age-dependent diurnal expression that correlates with age-related changes in genome-wide facultative heterochromatin
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ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE109856 | GEO | 2018/01/30
REPOSITORIES: GEO
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Project description:BackgroundDisrupted diurnal rhythms cause accelerated aging and an increased incidence in age-related disease and morbidity. The circadian clock governs cell physiology and metabolism by controlling transcription and chromatin. The goal of this study is to further understand the mechanism of age-related changes to circadian chromatin with a focus on facultative heterochromatin and diurnal non-coding RNAs.ResultsWe performed a combined RNA-seq and ChIP-seq at two diurnal time-points for three different age groups to examine the connection between age-related changes to circadian transcription and heterochromatin in neuronal tissue. Our analysis focused on uncovering the relationships between long non-coding RNA (lncRNA) and age-related changes to histone H3 lysine 9 tri-methylation (H3K9me3), in part because the Period (Per) complex can direct facultative heterochromatin and models of aging suggest age-related changes to heterochromatin and DNA methylation. Our results reveal that lncRNAs and circadian output change dramatically with age, but the core clock genes remain rhythmic. Age-related changes in clock-controlled gene (ccg) expression indicate there are age-dependent circadian output that change from anabolic to catabolic processes during aging. In addition, there are diurnal and age-related changes in H3K9me3 that coincide with changes in transcription.ConclusionsThe data suggest a model where some age-related changes in diurnal expression are partially attributed to age-related alterations to rhythmic facultative heterochromatin. The changes in heterochromatin are potentially mediated by changes in diurnal lncRNA creating an interlocked circadian-chromatin regulatory network that undergoes age-dependent metamorphosis.
| S-EPMC6206985 | biostudies-literature
Project description:The circadian rhythm controls timed choreography of gene expression to maintain normal cell physiology and metabolism. The predominant regulatory mechanism of the circadian rhythm is a transcriptional negative feedback loop that facilitates, and is facilitated by, circadian-regulated facultative heterochromatin. The long-term consequence of disrupted diurnal rhythm, or mutations in core clock genes, cause accelerated aging and an increased incidence in age-related diseases. To understand chromatin dynamics underlying age-related changes to circadian transcription, we performed a combined RNA-seq and ChIP-seq at two diurnal time-points for three different age groups. Our analysis focused on uncovering relationships between long non-coding RNA (lncRNA) and age-related changes to heterochromatin. We determined that the core clock genes maintain rhythmic expression regardless of age, but circadian output, including numerous lncRNAs, changes dramatically with age. In addition, there is both diurnal and age-related changes in Histone H3 lysine 9 tri-methylation (H3K9me3) that correlate with the changes in gene expression. Collectively, the data suggest a model where age-related changes in diurnal gene expression occur, in part, due to age-related redistribution of rhythmic facultative heterochromatin. Alterations in heterochromatin appear to be mediated by changes in diurnal lncRNA expression creating an interlocked circadian-chromatin regulatory network that undergoes age-dependent metamorphosis.
2018-01-30 | GSE109855 | GEO
Project description:The circadian rhythm controls timed choreography of gene expression to maintain normal cell physiology and metabolism. The predominant regulatory mechanism of the circadian rhythm is a transcriptional negative feedback loop that facilitates, and is facilitated by, circadian-regulated facultative heterochromatin. The long-term consequence of disrupted diurnal rhythm, or mutations in core clock genes, cause accelerated aging and an increased incidence in age-related diseases. To understand chromatin dynamics underlying age-related changes to circadian transcription, we performed a combined RNA-seq and ChIP-seq at two diurnal time-points for three different age groups. Our analysis focused on uncovering relationships between long non-coding RNA (lncRNA) and age-related changes to heterochromatin. We determined that the core clock genes maintain rhythmic expression regardless of age, but circadian output, including numerous lncRNAs, changes dramatically with age. In addition, there is both diurnal and age-related changes in Histone H3 lysine 9 tri-methylation (H3K9me3) that correlate with the changes in gene expression. Collectively, the data suggest a model where age-related changes in diurnal gene expression occur, in part, due to age-related redistribution of rhythmic facultative heterochromatin. Alterations in heterochromatin appear to be mediated by changes in diurnal lncRNA expression creating an interlocked circadian-chromatin regulatory network that undergoes age-dependent metamorphosis.
2018-01-30 | GSE109854 | GEO
Project description:Long non-coding RNAs have age-dependent diurnal expression that correlates with age-related changes in genome-wide facultative heterochromatin
| PRJNA432194 | ENA
Project description:Long non-coding RNAs have age-dependent diurnal expression that correlates with age-related changes in genome-wide facultative heterochromatin (ChIP-Seq data set)
| PRJNA432201 | ENA
Project description:Long non-coding RNAs have age-dependent diurnal expression that correlates with age-related changes in genome-wide facultative heterochromatin (RNA-Seq data set)
| PRJNA432202 | ENA
Project description:Psychosis is associated with chronic immune dysregulation. Many long non-coding RNAs (lncRNAs) display abnormal expression during activation of immune responses, and play a role in heterochromatic regulation of gene promoters. We have measured lncRNAs MEG3, PINT and GAS5, selected for their previously described association with heterochromatin. Peripheral blood mononuclear cells (PBMCs) were isolated from blood samples collected from 86 participants with a diagnosis of psychosis and 44 control participants. Expression was assessed in relation to diagnosis, illness acuity status, and treatment with antipsychotic medication. We observed diagnostic differences with MEG3, PINT and GAS5, and symptom acuity effect with MEG3 and GAS5. Medication effects were evident in those currently on treatment with antipsychotics when compared to drug-naïve participants. We observed that clinical diagnosis and symptom acuity predict selected lncRNA expression. Particular noteworthy is the differential expression of MEG3 in drug naïve participants compared to those treated with risperidone. Additionally, an in vitro cell model using M2tol macrophages was used to test the effects of the antipsychotic drug risperidone on the expression of these lncRNAs using quantitative real-time PCR (qRT-PCR). Significant but differential effects of risperidone were observed in M2tol macrophages indicating a clear ability of antipsychotic medications to modify lncRNA expression.
| S-EPMC6316406 | biostudies-literature
Project description:Long non-coding RNAs (lncRNAs) are transcripts longer than 200 bp with low or no protein-coding ability, which play essential roles in various biological processes in plants. Tobacco is an ideal model plant for studying nicotine biosynthesis and metabolism, and there is little research on lncRNAs in this field. Therefore, how to take advantage of the mature tobacco system to profoundly investigate the lncRNAs involved in the nicotine pathway is intriguing. By exploiting 549 public RNA-Seq datasets of tobacco, 30,212 lncRNA candidates were identified, including 24,084 large intervening non-coding RNAs (lincRNAs), 5,778 natural antisense transcripts (NATs) and 350 intronic non-coding RNAs (incRNAs). Compared with protein-coding genes, lncRNAs have distinct properties in terms of exon number, sequence length, A/U content, and tissue-specific expression pattern. lincRNAs showed an asymmetric evolutionary pattern, with a higher proportion (68.71%) expressed from the Nicotiana sylvestris (S) subgenome. We predicted the potential cis/trans-regulatory effects on protein-coding genes. One hundred four lncRNAs were detected as precursors of 30 known microRNA (miRNA) family members, and 110 lncRNAs were expected to be the potential endogenous target mimics for 39 miRNAs. By combining the results of weighted gene co-expression network analysis with the differentially expressed gene analysis of topping RNA-seq data, we constructed a sub-network containing eight lncRNAs and 25 nicotine-related coding genes. We confirmed that the expression of seven lncRNAs could be affected by MeJA treatment and may be controlled by the transcription factor NtMYC2 using a quantitative PCR assay and gene editing. The results suggested that lncRNAs are involved in the nicotine pathway. Our findings further deepened the understanding of the features and functions of lncRNAs and provided new candidates for regulating nicotine biosynthesis in tobacco.
| S-EPMC9892058 | biostudies-literature
Project description:BACKGROUND: Recent analysis of the mouse transcriptional data has revealed the existence of approximately 34,000 messenger-like non-coding RNAs (ml-ncRNAs). Whereas the functional properties of these ml-ncRNAs are beginning to be unravelled, no functional information is available for the large majority of these transcripts. RESULTS: A few ml-ncRNA have been shown to have genomic loci that overlap with microRNA loci, leading us to suspect that a fraction of ml-ncRNA may encode microRNAs. We therefore developed an algorithm (PriMir) for specifically detecting potential microRNA-encoding transcripts in the entire set of 34,030 mouse full-length ml-ncRNAs. In combination with mouse-rat sequence conservation, this algorithm detected 97 (80 of them were novel) strong miRNA-encoding candidates, and for 52 of these we obtained experimental evidence for the existence of their corresponding mature microRNA by microarray and stem-loop RT-PCR. Sequence analysis of the microRNA-encoding RNAs revealed an internal motif, whose presence correlates strongly (R2 = 0.9, P-value = 2.2 x 10(-16)) with the occurrence of stem-loops with characteristics of known pre-miRNAs, indicating the presence of a larger number microRNA-encoding RNAs (from 300 up to 800) in the ml-ncRNAs population. CONCLUSION: Our work highlights a unique group of ml-ncRNAs and offers clues to their functions.
| S-EPMC2410135 | biostudies-literature
Project description:Colorectal cancer is one of the most common causes of cancer-related deaths worldwide. Despite the advances in the knowledge of pathogenetic molecular mechanisms and the implementation of more effective drug treatments in recent years, the overall survival rate of patients remains unsatisfactory. The high death rate is mainly due to metastasis of cancer in about half of the cancer patients and the emergence of drug-resistant populations of cancer cells. Improved understanding of cancer molecular biology has highlighted the role of non-coding RNAs (ncRNAs) in colorectal cancer development and evolution. ncRNAs regulate gene expression through various mechanisms, including epigenetic modifications and interactions of long non-coding RNAs (lncRNAs) with both microRNAs (miRNAs) and proteins, and through the action of lncRNAs as miRNA precursors or pseudogenes. LncRNAs can also be detected in the blood and circulating ncRNAs have become a new source of non-invasive cancer biomarkers for the diagnosis and prognosis of colorectal cancer, as well as for predicting the response to drug therapy. In this review, we focus on the role of lncRNAs in colorectal cancer development, progression, and chemoresistance, and as possible therapeutic targets.
| S-EPMC9654895 | biostudies-literature