Paupar long non-coding RNA promotes KAP1 dependent chromatin changes and regulates olfactory bulb neurogenesis [gene expression]
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ABSTRACT:
PROVIDER: PRJNA432594 | ENA |
REPOSITORIES: ENA
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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: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: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 [CHIP-seq]
| PRJNA432593 | ENA
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.
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Project description:Olfactory sensory neurons distinguish a large variety of odor molecules and direct the information through their axons to the olfactory bulb, the first site for the processing of olfactory information in the brain. Olfaction is very important for most mammals for the maintenance of a good quality of life. Accumulating evidences endorse that olfactory sensory decline is connected with neurodegenerative disorders including schizophrenia, depression, multiple sclerosis, Huntington's, Alzheimer's and Parkinson's diseases. For several decades, neuroanatomical, volumetric, and histological approaches have been the gold standard techniques employed to characterize the olfactory bulb functionality. Diagnosis and treatment of olfactory dysfunction remain significant health care challenges to society. Novel strategies and clues that assist in the identification of biomarker and drug development for aid in the prevention and cure of neurological diseases are necessary. However, little attention has been focused specifically on the molecular composition of the olfactory bulb from the perspective of proteomics. To this end, an in-depth mapping of the olfactory bulb proteome was carried out using high resolution tandem mass spectrometry, revealing a repertoire of 7,754 proteins. A large proportion of the identified proteins were predicted to be involved in diverse biological processes including signal transduction, metabolism, transport, olfaction and protein synthesis. Pathway analysis of the identified proteins shows that, these proteins are predominantly involved in metabolic and neural processes, chromatin modeling, and synaptic vesicle transport associated with neuronal transmission. In total, our study offers valuable understandings into the molecular composition of the human olfactory bulb proteome that could possibly help neuroscience community to understand the olfactory bulb better and open avenues for intervention strategies for olfactory dysfunction in the future.
2017-08-23 | PXD005629 | Pride
Project description:The aim of this study was to use global gene expression profiling to define intrinsic molecular differences that distinguish olfactory ensheathing cells from mucosa (OM-OECs) from olfactory ensheathing cells from olfactory bulb (OB-OECs). 10,000 OECs from olfactory mucosa (OM) or olfactory bulb (OB) were isolated from 4 rats.
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Project description:Olfactory dysfunction is among the earliest features of Alzheimer´s disease (AD). Although neuropathological abnormalities have been detected in the olfactory bulb (OB), little is known about its dynamic biology. Here, OB- proteome analysis was performed across different AD stages using a label-free approach.
2018-01-16 | PXD005319 | Pride
Project description:Whole genome bisulfite-seq on 8 week adult mouse olfactory bulb For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
2021-11-04 | GSE187185 | GEO