ArticleThe Journal of biological chemistry2011
Macrophage-specific up-regulation of apolipoprotein E gene expression by STAT1 is achieved via long range genomic interactions.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Gene clusters linked to insulin resistance identified in a genome-wide study of the Taiwan Biobank population.Nature communications · 2025Article
- Reduction of APOE accounts for neurobehavioral deficits in fetal alcohol spectrum disorders.Molecular psychiatry · 2024Article
- Evidence that Alzheimer's Disease Is a Disease of Competitive Synaptic Plasticity Gone Awry.Journal of Alzheimer's disease : JAD · 2024Review
- Peroxisome Proliferator-Activated Receptor α in Lipoprotein Metabolism and Atherosclerotic Cardiovascular Disease.Biomedicines · 2023Review
- Apolipoprotein E derived from CD11ciScience · 2022Article
- Using Synthetic ApoC-II Peptides and nAngptl4 Fragments to Measure Lipoprotein Lipase Activity in Radiometric and Fluorescent Assays.Frontiers in cardiovascular medicine · 2022Article
- Postseptic Cognitive Impairment and Expression of APOE in Peripheral Blood: The Cognition After SepsiS (CASS) Observational Pilot Study.Journal of intensive care medicine · 2021Observational
- Microglia Impede Oligodendrocyte Generation in Aged Brain.Journal of inflammation research · 2021Article
- The Mechanism of Bisphenol A Atherogenicity Involves Apolipoprotein A-I Downregulation through NF-κB Activation.International journal of molecular sciences · 2019Article
- Apolipoprotein C1: Its Pleiotropic Effects in Lipid Metabolism and Beyond.International journal of molecular sciences · 2019Review
- The role of APOE in transgenic mouse models of AD.Neuroscience letters · 2019Review
- The Opposite Effect of c-Jun Transcription Factor on Apolipoprotein E Gene Regulation in Hepatocytes and Macrophages.International journal of molecular sciences · 2019Article
- Apolipoprotein E is an HIV-1-inducible inhibitor of viral production and infectivity in macrophages.PLoS pathogens · 2018Article
- Apolipoprotein C-II: New findings related to genetics, biochemistry, and role in triglyceride metabolism.Atherosclerosis · 2017Review
- Apolipoprotein E - A Multifunctional Protein with Implications in Various Pathologies as a Result of Its Structural Features.Computational and structural biotechnology journal · 2017Review
- Differential action of glucocorticoids on apolipoprotein E gene expression in macrophages and hepatocytes.PloS one · 2017Article
- Vitamin D interacts with Esr1 and Igf1 to regulate molecular pathways relevant to Alzheimer's disease.Molecular neurodegeneration · 2016Article
- High levels of homocysteine downregulate apolipoprotein E expression via nuclear factor kappa B.World journal of biological chemistry · 2016Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In atherogenesis, macrophage-derived apolipoprotein E (apoE) has an athero-protective role by a mechanism that is not fully understood. We investigated the regulatory mechanisms involved in the modulation of apoE expression in macrophages. The experiments showed that the promoters of all genes of the apoE/apoCI/apoCIV/apoCII gene cluster are enhanced by multienhancer 2 (ME.2), a regulatory region that is located 15.9 kb downstream of the apoE gene. ME.2 interacts with the apoE promoter in a macrophage-specific manner. Transient transfections in RAW 264.7 macrophages showed that the activity of ME.2 was strongly decreased by deletion of either 87 bp from the 5' end or 131 bp from the 3' end. We determined that the minimal fragment of this promoter that can be activated by ME.2 is the proximal -100/+73 region. The analysis of the deletion mutants of ME.2 revealed the importance of the 5' end of ME.2 in apoE promoter transactivation. Chromatin conformational capture assays demonstrated that both ME.2 and ME.1 physically interacted with the apoE promoter in macrophages. Our data showed that phorbol 12-myristate 13-acetate-induced differentiation of macrophages is accompanied by a robust induction of apoE and STAT1 expression. In macrophages (but not in hepatocytes), STAT1 up-regulated apoE gene expression via ME.2. The STAT1 binding site was located in the 174-182 region of ME.2. In conclusion, the specificity of the interactions between the two multienhancers (ME.1 and ME.2) and the apoE promoter indicates that these distal regulatory elements play an important role in the modulation of apoE gene expression in a cell-specific manner.
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