Similar Datasets
Project description:Many long non-coding RNAs (lncRNAs) are expressed during central nervous system (CNS) development, yet their in vivo roles and mechanisms of action remain poorly understood. Paupar, a CNS-expressed lncRNA, controls neuroblastoma cell growth by binding and modulating the activity of transcriptional regulatory elements in a genome-wide manner. We show here that the Paupar lncRNA directly binds KAP1, an essential epigenetic regulatory protein, and thereby regulates the expression of shared target genes important for proliferation and neuronal differentiation. Paupar promotes KAP1 chromatin occupancy and H3K9me3 deposition at a subset of distal targets, through the formation of a ribonucleoprotein complex containing Paupar, KAP1 and the PAX6 transcription factor. Paupar-KAP1 genome-wide co-occupancy reveals a fourfold enrichment of overlap between Paupar and KAP1 bound sequences, the majority of which also appear to associate with PAX6. Furthermore, both Paupar and Kap1 loss-of-function in vivo disrupt olfactory bulb neurogenesis. These observations provide important conceptual insights into the trans-acting modes of lncRNA-mediated epigenetic regulation and the mechanisms of KAP1 genomic recruitment, and identify Paupar and Kap1 as regulators of neurogenesis in vivo.
| S-EPMC5978383 | biostudies-literature
Project description:These data show that Paupar, a CNS expressed long non-coding RNA (lncRNA), directly and functionally associates with KAP1, an essential epigenetic regulatory protein. Transcriptome profiling of N2A cells identified 1,913 differentially expressed genes whose expression significantly changed (at a 5% false discovery rate [FDR]) greater than 1.4-fold (log2 fold change ≈ 0.5) upon KAP1 depletion. Examination of the intersection of KAP1 and Paupar transcriptional targets showed that Paupar and KAP1 control expression of a shared set of target genes that are enriched for regulators of neuronal function and cell cycle in N2A cells. Furthermore, CHART-seq and ChIP-seq derived Paupar-KAP1 genome-wide co-occupancy maps revealed a 4-fold enrichment of overlap between Paupar and KAP1 bound sequences on chromatin. This study also indicates that Paupar promotes KAP1 chromatin occupancy and H3K9me3 deposition at a subset of distal targets, through formation of a ribonucleoprotein complex containing Paupar, KAP1 and the PAX6 transcription factor. These observations provide important conceptual insights into the trans-acting modes of lncRNA-mediated epigenetic regulation and the mechanisms of KAP1 genomic recruitment.
2018-02-02 | GSE110031 | GEO
Project description:These data show that Paupar, a CNS expressed long non-coding RNA (lncRNA), directly and functionally associates with KAP1, an essential epigenetic regulatory protein. Transcriptome profiling of N2A cells identified 1,913 differentially expressed genes whose expression significantly changed (at a 5% false discovery rate [FDR]) greater than 1.4-fold (log2 fold change ≈ 0.5) upon KAP1 depletion. Examination of the intersection of KAP1 and Paupar transcriptional targets showed that Paupar and KAP1 control expression of a shared set of target genes that are enriched for regulators of neuronal function and cell cycle in N2A cells. Furthermore, CHART-seq and ChIP-seq derived Paupar-KAP1 genome-wide co-occupancy maps revealed a 4-fold enrichment of overlap between Paupar and KAP1 bound sequences on chromatin. This study also indicates that Paupar promotes KAP1 chromatin occupancy and H3K9me3 deposition at a subset of distal targets, through formation of a ribonucleoprotein complex containing Paupar, KAP1 and the PAX6 transcription factor. These observations provide important conceptual insights into the trans-acting modes of lncRNA-mediated epigenetic regulation and the mechanisms of KAP1 genomic recruitment.
2018-02-02 | GSE110032 | GEO
Project description:Paupar long non-coding RNA promotes KAP1 dependent chromatin changes and regulates olfactory bulb neurogenesis
| PRJNA432591 | ENA
Project description:Paupar long non-coding RNA promotes KAP1 dependent chromatin changes and regulates olfactory bulb neurogenesis [gene expression]
| PRJNA432594 | ENA
Project description:Paupar long non-coding RNA promotes KAP1 dependent chromatin changes and regulates olfactory bulb neurogenesis [CHIP-seq]
| PRJNA432593 | ENA
Project description:Although some long noncoding RNAs (lncRNAs) have been shown to regulate gene expression in cis, it remains unclear whether lncRNAs can directly regulate transcription in trans by interacting with chromatin genome-wide independently of their sites of synthesis. Here, we describe the genomically local and more distal functions of Paupar, a vertebrate-conserved and central nervous system-expressed lncRNA transcribed from a locus upstream of the gene encoding the PAX6 transcription factor. Knockdown of Paupar disrupts the normal cell cycle profile of neuroblastoma cells and induces neural differentiation. Paupar acts in a transcript-dependent manner both locally, to regulate Pax6, as well as distally by binding and regulating genes on multiple chromosomes, in part through physical association with PAX6 protein. Paupar binding sites are enriched near promoters and can function as transcriptional regulatory elements whose activity is modulated by Paupar transcript levels. Our findings demonstrate that a lncRNA can function in trans at transcriptional regulatory elements distinct from its site of synthesis to control large-scale transcriptional programmes.
| S-EPMC3983687 | biostudies-literature
Project description:Neural stem cell populations generate a wide spectrum of neuronal and glial cell types in a highly ordered fashion. MicroRNAs are essential regulators of this process. T-UCstem1 is a long non-coding RNA containing an ultraconserved element, and in vitro analyses in pluripotent stem cells provided evidence that it regulates the balance between proliferation and differentiation. Here we investigate the in vivo function of T-UCstem1. We show that T-UCstem1 is expressed in the forebrain neurogenic lineage that generates interneurons for the postnatal olfactory bulb. Gain of function in neural stem cells increased progenitor proliferation at the expense of neuron production, whereas knockdown had the opposite effect. This regulatory function is mediated by its interaction with miR-9-3p and miR-9-5p. Based thereon, we propose a mechanistic model for the role of T-UCstem1 in the dynamic regulation of neural progenitor proliferation during neurogenesis.
| S-EPMC7562942 | biostudies-literature
Project description:Age-related decline in olfactory function affects the quality of life in elderly people and also potentially represents an early clinical symptom of neurodegenerative disorder. Olfactory bulb (OB) plays a central role in olfactory information transmitting and signal processing. The mechanisms underlying this impairment remain unclear. In the current study, microarray was used to investigate differentially expressed protein coding genes (PCGs) and long non-coding RNAs (lncRNAs) in OBs from three groups of mice of different ages (2 months-old young adults, 6 months-old mature adults and 20 months-old aged adults), for their potential roles in olfactory impairment. Gene Ontology and pathway analysis results showed that the differentially expressed PCGs in the OBs from aged mice were mainly associated with signal transduction, regulation of gene expression and cellular microenvironment. Similarly, gene set enrichment analysis identified two differentially and inversely expressed lncRNAs (NONMMUT004524 and NONMMUT000384), both of which were significantly associated with neuroactive ligand-receptor interaction pathway in the OBs of aged mice. These findings suggest that a decline of olfactory function in aged mice may be linked to differential expression of specific lncRNAs and their potentially adverse effects on the neuroactive ligand-receptor interaction pathway in the OB.
| S-EPMC5437011 | biostudies-literature
Project description:Although some long noncoding RNAs (lncRNAs) have been shown to regulate gene expression in cis, it remains unclear whether lncRNAs can directly regulate transcription in trans by interacting with chromatin genome-wide independently of their sites of synthesis. Here, we describe the genomically local and more distal functions of Paupar, a vertebrate-conserved and central nervous system-expressed lncRNA transcribed from a locus upstream of the gene encoding the Pax6 transcription factor. Knockdown of Paupar disrupts the normal cell cycle profile of neuroblastoma cells and induces neuronal differentiation. Paupar acts in a transcript-dependent manner both locally, to regulate Pax6, as well as distally by binding and regulating genes on multiple chromosomes, in part through physical association with Pax6 protein. Paupar binding sites are enriched near promoters and can function as transcriptional regulatory elements whose activity is modulated by Paupar transcript levels. Our findings demonstrate that a lncRNA can function in trans at transcriptional regulatory elements distinct from its site of synthesis to control large-scale transcriptional programmes. N2A cells transfected with a non-targeting control vector were compared to N2A cells transfected with a Paupar knockdown construct. Three biological replicates of each condition were analysed on Affymetrix GeneChip Mouse Gene 1.0 ST Arrays.
2013-11-21 | E-GEOD-52569 | biostudies-arrayexpress