Similar Datasets
Project description:To better understand the regulatory roles of ApoE in neurogenesis, we differentiated isogenic control and ApoE-/- human neural stem cells (NSC) into mature cortical neurons and cultured them for additional three weeks. In this study, we found that ApoE is only expressed in control NSC and neural progenitor cell (NPC) stages, but not in mature neurons, suggesting that ApoE may epigenetically regulate the integrity and maintenance of the mature neurons. Mechanistic studies revealed that absence of ApoE in NSC led to upregulation of certain microRNAs, including miR-199a-5p. These microRNAs targeted EZH1 to reduce its protein expression, resulting in the lower level of repressive H3K27me3 marks in ApoE-/- NPC and mature neurons. Chromatin immunoprecipitation experiments suggests that the lower level of H3K27me3 at various extracellular matrix organization and angiogenesis genes is responsible for their higher expression and aberrant phenotypes observed in ApoE-/- neurons. Taken together, our results indicate that ApoE maintains pure population of mature neurons via H3K27me3-mediated repression of genes that drive non-neuronal cell proliferation in NPC stage.
2024-01-29 | GSE198230 | GEO
Project description:To better understand the regulatory roles of ApoE in neurogenesis, we differentiated isogenic control and ApoE-/- human neural stem cells (NSC) into mature cortical neurons and cultured them for additional three weeks. In this study, we found that ApoE is only expressed in control NSC and neural progenitor cell (NPC) stages, but not in mature neurons, suggesting that ApoE may epigenetically regulate the integrity and maintenance of the mature neurons. Mechanistic studies revealed that absence of ApoE in NSC led to upregulation of certain microRNAs, including miR-199a-5p. These microRNAs targeted EZH1 to reduce its protein expression, resulting in the lower level of repressive H3K27me3 marks in ApoE-/- NPC and mature neurons. Chromatin immunoprecipitation experiments suggests that the lower level of H3K27me3 at various extracellular matrix organization and angiogenesis genes is responsible for their higher expression and aberrant phenotypes observed in ApoE-/- neurons. Taken together, our results indicate that ApoE maintains pure population of mature neurons via H3K27me3-mediated repression of genes that drive non-neuronal cell proliferation in NPC stage.
2024-01-29 | GSE198228 | GEO
Project description:ApoE maintains neuronal integrity via miRNA and H3K27me3-mediated repression
| PRJNA814271 | ENA
Project description:ApoE maintains neuronal integrity via miRNA and H3K27me3-mediated repression [miRNA-seq]
| PRJNA814267 | ENA
Project description:ApoE maintains neuronal integrity via miRNA and H3K27me3-mediated repression [RNA-seq]
| PRJNA814246 | ENA
Project description:Maintenance of vascular integrity is required for embryogenesis and organ homeostasis. However, the gene expression programs that stabilize blood vessels are poorly understood. Here, we show that the histone methyltransferase Ezh2 maintains integrity of the developing vasculature by repressing a transcriptional program that activates expression of Mmp9. Inactivation of Ezh2 in developing mouse endothelium caused embryonic lethality with compromised vascular integrity and increased extracellular matrix degradation. Genome-wide approaches showed that Ezh2 targets Mmp9 and its activators Fosl1 and Klf5. In addition, we uncovered Creb3l1 as an Ezh2 target that directly activates Mmp9 gene expression in the endothelium. Furthermore, genetic inactivation of Mmp9 rescued vascular integrity defects in Ezh2-deficient embryos. Thus, epigenetic repression of Creb3l1, Fosl1, Klf5 and Mmp9 by Ezh2 in endothelial cells maintains the integrity of the developing vasculature, potentially linking this transcriptional network to diseases with compromised vascular integrity.
| S-EPMC4302930 | biostudies-literature
Project description:Since their discovery 20 years ago, miRNAs have attracted much attention from all areas of biology. These short (∼22 nt) non-coding RNA molecules are highly conserved in evolution and are present in nearly all eukaryotes. They have critical roles in virtually every cellular process, particularly determination of cell fate in development and regulation of the cell cycle. Although it has long been known that miRNAs bind to mRNAs to trigger translational repression and degradation, there had been much debate regarding their precise mode of action. It is now believed that translational control is the primary event, only later followed by mRNA destabilisation. This review will discuss the most recent advances in our understanding of the molecular underpinnings of miRNA-mediated repression. Moreover, we highlight the multitude of regulatory mechanisms that modulate miRNA function.
| S-EPMC4262769 | biostudies-other
Project description:In mammalian cells, the Golgi reassembly stacking protein of 65 kDa (GRASP65) has been implicated in both Golgi stacking and ribbon linking by forming trans-oligomers. To better understand its function and regulation, we used biochemical methods to identify the DnaJ homolog subfamily A member 1 (DjA1) as a novel GRASP65-binding protein. In cells, depletion of DjA1 resulted in Golgi fragmentation, short and improperly aligned cisternae, and delayed Golgi reassembly after nocodazole washout. In vitro, immunodepletion of DjA1 from interphase cytosol reduced its activity to enhance GRASP65 oligomerization and Golgi membrane fusion, while adding purified DjA1 enhanced GRASP65 oligomerization. DjA1 is a cochaperone of Heat shock cognate 71-kDa protein (Hsc70), but the activity of DjA1 in Golgi structure formation is independent of its cochaperone activity or Hsc70, rather, through DjA1-GRASP65 interaction to promote GRASP65 oligomerization. Thus, DjA1 interacts with GRASP65 to enhance Golgi structure formation through the promotion of GRASP65 trans-oligomerization.
| S-EPMC6594443 | biostudies-literature
Project description:Recent studies have shown that long noncoding RNAs (lncRNAs) are critical regulators in the central nervous system (CNS). However, their roles in the cerebellum are currently unclear. In this work, we identified the isoform 204 of lncRNA Gm2694 (designated as lncRNA-Promoting Methylation (lncRNA-PM)) is highly expressed in the cerebellum and derived from the antisense strand of the upstream region of Cerebellin-1 (Cbln1), a well-known critical cerebellar synaptic organizer. LncRNA-PM exhibits similar spatiotemporal expression pattern as Cbln1 in the postnatal mouse cerebellum and activates the transcription of Cbln1 through Pax6/Mll1-mediated H3K4me3. In mouse cerebellum, lncRNA-PM, Pax6/Mll1, and H3K4me3 are all associated with the regulatory regions of Cbln1. Knockdown of lncRNA-PM in cerebellum causes deficiencies in Cbln1 expression, cerebellar synaptic integrity, and motor function. Together, our work reveals an lncRNA-mediated transcriptional activation of Cbln1 through Pax6-Mll1-H3K4me3 and provides novel insights of the essential roles of lncRNA in the cerebellum.
| S-EPMC8219131 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-01-26 | GSE151440 | GEO