An Epigenetics-Based Hypothesis of Autoantigen Development in Systemic Lupus Erythematosus
Currently, we have a limited understanding of mechanisms leading to systemic lupus erythematosus, but we know that genetics, environmental factors, and epigenetics contribute to the disease. One common aspect of the various environmental triggers is that they can cause cellular stress. When extraord...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-04-01
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| Series: | Epigenomes |
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| Online Access: | https://www.mdpi.com/2075-4655/4/2/6 |
| _version_ | 1797569803301421056 |
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| author | Wesley Brooks |
| author_facet | Wesley Brooks |
| author_sort | Wesley Brooks |
| collection | DOAJ |
| description | Currently, we have a limited understanding of mechanisms leading to systemic lupus erythematosus, but we know that genetics, environmental factors, and epigenetics contribute to the disease. One common aspect of the various environmental triggers is that they can cause cellular stress. When extraordinary stress occurs, such as viral activation, a cell’s response can include increased nucleolar volume and activity to produce more machinery (e.g., ribosomes) to help the cell recover. However, nucleolar expansion can disrupt the epigenetic control in neighboring heterochromatin that comprises the nucleolar shell. This disruption can open underlying vulnerabilities that provoke an autoimmune reaction. Here, we review the “X chromosome-nucleolus nexus” hypothesis, which explains how nucleolar stress can disrupt epigenetically silenced chromatin, especially the neighboring inactive X chromosome (aka the nucleolar satellite). Chromatin disruption can lead to the expression of sequestered DNA, such as <i>Alu</i> elements and fully functional <i>LINE-1</i> reverse transcriptase genes. In addition, <i>Alu</i> transcripts can disrupt the nucleolar structural integrity, leading to nucleolar disintegration. Such disintegration can leave nucleolar components and products in autoantigenic forms, such as abnormal conformations or incomplete macromolecular assemblies. Recent research on DNA sensing pathways can now be incorporated into the hypothesis to provide further details explaining how autoantibodies to endogenous nucleic acids arise. |
| first_indexed | 2024-03-10T20:16:43Z |
| format | Article |
| id | doaj.art-c6767f617744465fb1a990900d3ed36d |
| institution | Directory Open Access Journal |
| issn | 2075-4655 |
| language | English |
| last_indexed | 2024-03-10T20:16:43Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Epigenomes |
| spelling | doaj.art-c6767f617744465fb1a990900d3ed36d2023-11-19T22:31:00ZengMDPI AGEpigenomes2075-46552020-04-0142610.3390/epigenomes4020006An Epigenetics-Based Hypothesis of Autoantigen Development in Systemic Lupus ErythematosusWesley Brooks0Department of Chemistry, University of South Florida, Tampa, FL 33620, USACurrently, we have a limited understanding of mechanisms leading to systemic lupus erythematosus, but we know that genetics, environmental factors, and epigenetics contribute to the disease. One common aspect of the various environmental triggers is that they can cause cellular stress. When extraordinary stress occurs, such as viral activation, a cell’s response can include increased nucleolar volume and activity to produce more machinery (e.g., ribosomes) to help the cell recover. However, nucleolar expansion can disrupt the epigenetic control in neighboring heterochromatin that comprises the nucleolar shell. This disruption can open underlying vulnerabilities that provoke an autoimmune reaction. Here, we review the “X chromosome-nucleolus nexus” hypothesis, which explains how nucleolar stress can disrupt epigenetically silenced chromatin, especially the neighboring inactive X chromosome (aka the nucleolar satellite). Chromatin disruption can lead to the expression of sequestered DNA, such as <i>Alu</i> elements and fully functional <i>LINE-1</i> reverse transcriptase genes. In addition, <i>Alu</i> transcripts can disrupt the nucleolar structural integrity, leading to nucleolar disintegration. Such disintegration can leave nucleolar components and products in autoantigenic forms, such as abnormal conformations or incomplete macromolecular assemblies. Recent research on DNA sensing pathways can now be incorporated into the hypothesis to provide further details explaining how autoantibodies to endogenous nucleic acids arise.https://www.mdpi.com/2075-4655/4/2/6epigeneticslupuspolyaminesX chromosomenucleolusautoantigens |
| spellingShingle | Wesley Brooks An Epigenetics-Based Hypothesis of Autoantigen Development in Systemic Lupus Erythematosus Epigenomes epigenetics lupus polyamines X chromosome nucleolus autoantigens |
| title | An Epigenetics-Based Hypothesis of Autoantigen Development in Systemic Lupus Erythematosus |
| title_full | An Epigenetics-Based Hypothesis of Autoantigen Development in Systemic Lupus Erythematosus |
| title_fullStr | An Epigenetics-Based Hypothesis of Autoantigen Development in Systemic Lupus Erythematosus |
| title_full_unstemmed | An Epigenetics-Based Hypothesis of Autoantigen Development in Systemic Lupus Erythematosus |
| title_short | An Epigenetics-Based Hypothesis of Autoantigen Development in Systemic Lupus Erythematosus |
| title_sort | epigenetics based hypothesis of autoantigen development in systemic lupus erythematosus |
| topic | epigenetics lupus polyamines X chromosome nucleolus autoantigens |
| url | https://www.mdpi.com/2075-4655/4/2/6 |
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