LncRNA HOXA-AS2 regulates microglial polarization via recuitment of PRC2 and epigenetic modification of PGC-1α expression
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ABSTRACT:
PROVIDER: PRJNA735207 | ENA |
REPOSITORIES: ENA
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| S-EPMC8436538 | biostudies-literature
Project description:Glioblastoma multiform account for about half of all gliomas and are the most deadly and aggressive forms. Its therapeutic resistance and tumor relapse rely on a subpopulation of cells, the so-called Glioma-stem Cells (GSCs). Here, we investigated for the role of the long non-coding RNA HOXA-AS2 in GSC biology by conducting descriptive and functional analyses of glioma samples classified according to their isocitrate dehydrogenase (IDH1) gene mutation status, and of glioma stem cells. We found that HOXA-AS2 is overexpressed only in aggressive (IDHwt) glioma and GSC. Sh-RNA-based depletion of HOXA-AS2 affects GSC both at the cellular and molecular levels with a decrease in proliferation and altered expression of several hundreds of their genes. Integrative analysis revealed that these changes is expression are not associated to changes in DNA methylation or chromatin signature at the promoter of most deregulated genes following HOXA-AS2 silencing in GSC, supporting a post-transcriptional regulation. In addition, transcription factor motif enrichment and correlation analyses sustained that HOXA-AS2 affect, directly or indirectly, expression of key transcription factors of GCS biology, including E2F8, E2F1, STAT1 and ATF3 to, in fine, contributes to their pathological status by promoting proliferation and modulating the inflammation pathway of Glioma Stem Cell.
2022-04-15 | GSE199031 | GEO
Project description:Glioblastoma multiform account for about half of all gliomas and are the most deadly and aggressive forms. Its therapeutic resistance and tumor relapse rely on a subpopulation of cells, the so-called Glioma-stem Cells (GSCs). Here, we investigated for the role of the long non-coding RNA HOXA-AS2 in GSC biology by conducting descriptive and functional analyses of glioma samples classified according to their isocitrate dehydrogenase (IDH1) gene mutation status, and of glioma stem cells. We found that HOXA-AS2 is overexpressed only in aggressive (IDHwt) glioma and GSC. Sh-RNA-based depletion of HOXA-AS2 affects GSC both at the cellular and molecular levels with a decrease in proliferation and altered expression of several hundreds of their genes. Integrative analysis revealed that these changes is expression are not associated to changes in DNA methylation or chromatin signature at the promoter of most deregulated genes following HOXA-AS2 silencing in GSC, supporting a post-transcriptional regulation. In addition, transcription factor motif enrichment and correlation analyses sustained that HOXA-AS2 affect, directly or indirectly, expression of key transcription factors of GCS biology, including E2F8, E2F1, STAT1 and ATF3 to, in fine, contributes to their pathological status by promoting proliferation and modulating the inflammation pathway of Glioma Stem Cell.
2022-04-15 | GSE199030 | GEO
Project description:Transcriptional coactivator PGC-1α and its splice variant NT-PGC-1α play crucial roles in regulating cold-induced thermogenesis in brown adipose tissue (BAT). PGC-1α and NT-PGC-1α are highly induced by cold in BAT and subsequently bind to and coactivate many different transcription factors to regulate expression of genes involved in mitochondrial biogenesis, fatty acid oxidation, respiration and thermogenesis. To identify the complete repertoire of PGC-1α and NT-PGC-1α target genes in BAT, we analyzed genome-wide DNA-binding and gene expression profiles. We find that PGC-1α-/NT-PGC-1α binding broadly associates with cold-mediated transcriptional activation. In addition to their known target genes in mitochondrial biogenesis, fatty acid oxidation, respiration and thermogenesis, PGC-1α and NT-PGC-1α target to a broad spectrum of genes involved in diverse biological pathways including ubiquitin-dependent protein catabolism, ribonucleoprotein complex biosynthesis, phospholipid biosynthesis, angiogenesis, glycogen metabolism, phosphorylation, and autophagy. Our findings expand the number of genes and biological pathways that may be regulated by PGC-1α and NT-PGC-1α and provide further insight into the transcriptional regulatory network in which PGC-1α and NT-PGC-1α coordinate a comprehensive transcriptional response in BAT in response to cold.
2018-05-22 | GSE110055 | GEO
Project description:Transcriptional coactivator PGC-1α and its splice variant NT-PGC-1α play crucial roles in regulating cold-induced thermogenesis in brown adipose tissue (BAT). PGC-1α and NT-PGC-1α are highly induced by cold in BAT and subsequently bind to and coactivate many different transcription factors to regulate expression of genes involved in mitochondrial biogenesis, fatty acid oxidation, respiration and thermogenesis. To identify the complete repertoire of PGC-1α and NT-PGC-1α target genes in BAT, we analyzed genome-wide DNA-binding and gene expression profiles. We find that PGC-1α-/NT-PGC-1α binding broadly associates with cold-mediated transcriptional activation. In addition to their known target genes in mitochondrial biogenesis, fatty acid oxidation, respiration and thermogenesis, PGC-1α and NT-PGC-1α target to a broad spectrum of genes involved in diverse biological pathways including ubiquitin-dependent protein catabolism, ribonucleoprotein complex biosynthesis, phospholipid biosynthesis, angiogenesis, glycogen metabolism, phosphorylation, and autophagy. Our findings expand the number of genes and biological pathways that may be regulated by PGC-1α and NT-PGC-1α and provide further insight into the transcriptional regulatory network in which PGC-1α and NT-PGC-1α coordinate a comprehensive transcriptional response in BAT in response to cold.
2018-05-22 | GSE110053 | GEO
Project description:Glioblastoma multiform account for about half of all gliomas and are the most deadly and aggressive forms. Its therapeutic resistance and tumor relapse rely on a subpopulation of cells, the so-called Glioma-stem Cells (GSCs). Here, we investigated for the role of the long non-coding RNA HOXA-AS2 in GSC biology by conducting descriptive and functional analyses of glioma samples classified according to their isocitrate dehydrogenase (IDH1) gene mutation status, and of glioma stem cells. We found that HOXA-AS2 is overexpressed only in aggressive (IDHwt) glioma and GSC. Sh-RNA-based depletion of HOXA-AS2 affects GSC both at the cellular and molecular levels with a decrease in proliferation and altered expression of several hundreds of their genes. Integrative analysis revealed that these changes is expression are not associated to changes in DNA methylation or chromatin signature at the promoter of most deregulated genes following HOXA-AS2 silencing in GSC, supporting a post-transcriptional regulation. In addition, transcription factor motif enrichment and correlation analyses sustained that HOXA-AS2 affect, directly or indirectly, expression of key transcription factors of GCS biology, including E2F8, E2F1, STAT1 and ATF3 to, in fine, contributes to their pathological status by promoting proliferation and modulating the inflammation pathway of Glioma Stem Cell.
2022-04-15 | GSE199032 | GEO
Project description:The β-adrenergic receptor signaling pathway is a major component of adaptive thermogenesis in brown and white adipose tissue during cold acclimation. The β-AR activation highly induces transcriptional coactivator PGC-1α and its splice variant N-terminal (NT)-PGC-1α, promoting the transcription program of mitochondrial biogenesis and thermogenesis. In the present study, we evaluated the role of NT-PGC-1α in brown adipocyte energy metabolism by genome-wide profiling of NT-PGC-1α-responsive genes. Canonical pathway analysis revealed that a number of genes upregulated by NT-PGC-1α are highly enriched in mitochondrial pathways including fatty acid transport and β-oxidation, TCA cycle and electron transport system, thus reinforcing the crucial role of NT-PGC-1α in the enhancement of mitochondrial function. Moreover, gene expression profiling of NT-PGC-1α revealed activation of distinct metabolic pathways such as glucose, lipid and nucleotide metabolism and of signaling pathways such as RAR and PPAR-γ/RXRα activation in brown adipocytes. Together, our data strengthen our previous findings that NT-PGC-1α is a key regulator of mitochondrial oxidative metabolism and thermogenesis in brown adipocytes and further suggest that NT-PGC-1α influences a broader spectrum of thermogenic processes to meet cellular needs for adaptive thermogenesis. Two samples from two groups: NT-PGC-1α overexpression and empty vector. There are technical replicates (A and B) for each group. Two RNA samples were pooled for each group.
2015-08-07 | E-GEOD-71774 | biostudies-arrayexpress
Project description:We profiled the expressioon of lncRNAs in the peripheral blood mononuclear cells (PBMCs) of PD patients and healthy controls. the enrichment of lncRNAs from PBMCs using Arraystar Human lncRNAs chip (Arraystar).
2021-09-22 | GSE176167 | GEO
Project description:The peroxisome-proliferator-activated receptor-γ coactivator-1α (PGC-1α) integrates environmental cues by controlling complex transcriptional networks in various metabolically active tissues. However, it is unclear how a transcriptional coregulator coordinates dynamic biological programs in response to multifaceted stimuli such as endurance training or fasting. Here, we discovered a central function of the poorly understood C-terminal domain (CTD) of PGC-1α to bind RNAs and assemble multi-protein complexes. Surprisingly, in addition to controlling the coupling of transcription and processing of target genes, RNA binding is indispensable for the recruitment of PGC-1α to chromatin into liquid-like nuclear condensates, which compartmentalize and regulate active transcription. These results demonstrate a hitherto unsuspected molecular mechanism by which complexity in the regulation of large transcriptional networks by PGC-1α is achieved. These findings are not only essential for the basic understanding of transcriptional coregulator-driven control of biological programs, but will also help to devise new strategies to modulate these processes in pathological contexts in which PGC-1α function is dysregulated, such as type 2 diabetes, cardiovascular diseases or skeletal muscle wasting.
2021-08-19 | PXD026725 | Pride
Project description:PGC-1α in microglia protects against ischemia-induced brain damage in mice. The data suggest that microglia-specific PGC-1α play a key role in limiting ischemia-induced brain damage and potently participates in regulating microglial function. To further clarify the mechanism of PGC-1α, we conducted chromatin immunoprecipitation-sequencing (ChIP-Seq) analysis to identify the targets of PGC-1α in microglia from mPGC-1α mice at 24 h after ischemic stroke. KEGG pathway analysis of these genes identified the mitophagy signaling pathway as one of the most highly enriched pathways. Finally, we demonstrated that PGC-1α induces mitophagy by regulating ULK1 expression in an ERRα-dependent manner, thereby reducing neuroinflammatory reactions.
2021-01-27 | GSE165564 | GEO