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Epigenetic regulation of macrophage cholesterol efflux and atherogenesis by a long noncoding RNA

ABSTRACT: Epigenetic regulation of macrophage cholesterol efflux and atherogenesis by a long noncoding RNA

PROVIDER: PRJNA422096 | ENA |

REPOSITORIES: ENA

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Epigenetic regulation of macrophage cholesterol efflux and atherogenesis by a long noncoding RNA

Project description:Nuclear receptors are important conduits between environmental cues and gene expression, but the molecular events governing spatial variation in their responses remain poorly understood. Here we outline an important role for a non-coding RNA in modulating the cell type-specific actions of the cholesterol-activated nuclear receptor LXR. LXR regulates the expression of genes involved in responses to excess cholesterol and has been causally linked to the pathogenesis and treatment of prevention and atherosclerosis in animals. We identify the lncRNA MeXis as an amplifier of LXR-dependent transcription of the critical cholesterol efflux gene Abca1. MeXis interacts with and guides the promoter binding of the nuclear receptor transcriptional coactivator DDX17. Loss of MeXis in murine immune cells has a marked impact on chromosome architecture at the Abca1 locus, impairs cellular responses to cholesterol overload, and accelerates the development of atherosclerosis. Our findings define MeXis as a lncRNA gatekeeper that modifies the actions of LXR in lipid-dependent control of macrophage gene expression. This has important implications for mechanisms that underlie spatial activation patterns of nuclear receptors. Our work opens a new gateway to targeting reverse cholesterol transport since it is conceivable that therapeutic approaches that enhance MeXis activity might reduce foam cell formation and atherogenesis.

2018-01-26 | GSE97207 | GEO

Transcriptional regulation of macrophage cholesterol efflux and atherogenesis by a long noncoding RNA

Project description:Nuclear receptors are important conduits between environmental cues and gene expression, but the molecular events governing spatial variation in their responses remain poorly understood. Here we outline an important role for a non-coding RNA in modulating the cell type-specific actions of the cholesterol-activated nuclear receptor LXR. LXR regulates the expression of genes involved in responses to excess cholesterol and has been causally linked to the pathogenesis and treatment of prevention and atherosclerosis in animals. We identify the lncRNA MeXis as an amplifier of LXRdependent transcription of the critical cholesterol efflux gene Abca1. MeXis interacts with and guides the promoter binding of the nuclear receptor transcriptional coactivator DDX17. Loss of MeXis in murine immune cells has a marked impact on chromosome architecture at the Abca1 locus, impairs cellular responses to cholesterol overload, and accelerates the development of atherosclerosis. Our findings define MeXis as a lncRNA gatekeeper that modifies the actions of LXR in lipid-dependent control of macrophage gene expression. This has important implications for mechanisms that underlie spatial activation patterns of nuclear receptors. Our work opens a new gateway to targeting reverse cholesterol transport since it is conceivable that therapeutic approaches that enhance MeXis activity might reduce foam cell formation and atherogenesis

2018-01-26 | GSE98910 | GEO

Epigenetic regulation of macrophage cholesterol efflux and atherogenesis by a long noncoding RNA

Project description:In this work we show that the LXR target lncRNA MeXis plays an important role in cellular responses to cholesterol overload In this experiment we use array technology to decipher the contribution of loss of MeXis from mouse primary peritoneal macrophages.

2018-01-26 | GSE107977 | GEO

Transcriptional regulation of macrophage cholesterol efflux and atherogenesis by a long noncoding RNA.

Project description:Nuclear receptors regulate gene expression in response to environmental cues, but the molecular events governing the cell type specificity of nuclear receptors remain poorly understood. Here we outline a role for a long noncoding RNA (lncRNA) in modulating the cell type-specific actions of liver X receptors (LXRs), sterol-activated nuclear receptors that regulate the expression of genes involved in cholesterol homeostasis and that have been causally linked to the pathogenesis of atherosclerosis. We identify the lncRNA MeXis as an amplifier of LXR-dependent transcription of the gene Abca1, which is critical for regulation of cholesterol efflux. Mice lacking the MeXis gene show reduced Abca1 expression in a tissue-selective manner. Furthermore, loss of MeXis in mouse bone marrow cells alters chromosome architecture at the Abca1 locus, impairs cellular responses to cholesterol overload, and accelerates the development of atherosclerosis. Mechanistic studies reveal that MeXis interacts with and guides promoter binding of the transcriptional coactivator DDX17. The identification of MeXis as a lncRNA modulator of LXR-dependent gene expression expands understanding of the mechanisms underlying cell type-selective actions of nuclear receptors in physiology and disease.

| S-EPMC5839972 | biostudies-literature

Mus musculus

Project description:Epigenetic regulation of macrophage cholesterol efflux and atherogenesis by a long noncoding RNA

| PRJNA380956 | ENA

Mus musculus

Project description:Transcriptional regulation of macrophage cholesterol efflux and atherogenesis by a long noncoding RNA

| PRJNA386898 | ENA

Metabolomics Workbench ST000681 - GNPS - Retinal tissue knockout to study efflux of cholesterol (AGCA1/G1 double KO - TY and LysM cre)

Project description:ABCA1 and AGCG1, which is important gene to efflux the cholesterol from the cell/tissue, are knocked out in specific retinal tissue. T:RPE specific, L:macrophage specific.

2018-08-02 | MSV000082705 | GNPS

Targeting Epsins by nanotherapy regulates lipid metabolism and promotes ABCG1-mediated cholesterol efflux to fortify atheroma regression [scRNA-seq]

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2022-11-26 | GSE214413 | GEO

Targeting Epsins by nanotherapy regulates lipid metabolism and promotes ABCG1-mediated cholesterol efflux to fortify atheroma regression [RNA-seq]

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Gene expression profile at single cell level of lung-tumor bearing KrasG12D mice with or without defective cholesterol efflux

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2023-06-01 | GSE226597 | GEO

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