An Epigenetics-Based Hypothesis of Autoantigen Development in Systemic Lupus Erythematosus
Abstract
:1. Introduction—The Complexity of Autoimmune Diseases
2. Components of the “X Chromosome-Nucleolus Nexus” Hypothesis
2.1. The Hypothesis in Brief
2.2. The Nucleolus: Functions and Stress
2.3. Polyamines
2.4. The Inactive X Chromosome
3. The “X Chromosome-Nucleolus Nexus” Hypothesis in Action
3.1. Disruption of the Inactive X Chromosome
3.2. Disruption of the Nucleolus
3.3. New Developments in the “X Chromosome-Nucleolus Nexus” Hypothesis
4. Conclusions
Funding
Acknowledgments
Conflicts of Interest
References
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Autoantigen | Function/Complex | Occurrence (% in SLE) | Reference |
---|---|---|---|
Nucleolin | Nucleolar structural integrity | >50 | [26] |
U1RNP | Spliceosome component | 40 | [26] |
U1RNA | Spliceosome component | <5 | [26] |
Sm epitopes | Spliceosome proteins | 25 | [26] |
SSA/Ro | RNA pol III chaperone | 40–50 | [26] |
SSB/La | RNA pol III chaperone and termination | 15 | [26] |
Ribosomal P proteins | Phospho proteins, bind 28S RNA | 12–16 | [27] |
Ku | dsDNA break repair | 20–40 | [26] |
Cardiolipin | Similar epitopes to nucleophosmin | 20–40 | [26] |
Centromere components | CENP-B and others | ~6 | [26] |
Lamins | Complexed with nucleolin | unknown | [28] |
Gene/Site | Name | Location | Potential Issue | Reference |
---|---|---|---|---|
Alu elements | Short Interspersed Elements | Enriched in PAR1 | Disruption | [15] |
FRAXB | Fragile Site B | Xp22 | Latent viruses, DNA damage | [89] |
(hot) LINE-1 | Long Interspersed Elements | Xp22 | Reverse transcription | [15] |
SMS | Spermine Synthase | Xp22 | Polyamine dysregulation | [15] |
SAT1 | Spermidine/Spermine N1 Acetyltransferase | Xp22 | Polyamine dysregulation | [15] |
TLR7 | Toll-like Receptor 7 | Xp22 | Overexpression | [90] |
FOXP3 | Forkhead Box P3 | Xp11 | T-cell dysregulation | [91] |
CXCR3 | C-X-C motif chemokine receptor 3 | Xq13 | Overexpression | [92] |
FRAXC | Fragile Site C | Xq22 | Latent viruses, DNA damage | [89] |
CD40L | Cluster of differentiation 40 ligand | Xq24 | Overexpression | [90] |
HERV-w | Human endogenous retrovirus w | Xq22 | Dysregulation | [93,94] |
FRAXD | Fragile Site D | Xq27 | Latent viruses, DNA damage | [89] |
MeCP2 | Methyl-CpG-binding protein 2 | Xq28 | DNA methylation dysregulation | [95] |
IRAK1 | Interleukin-1 receptor associated kinase-1 | Xq28 | Checkpoint dysregulation | [96] |
FRAXA | Fragile Site A | Xq28 | Latent viruses, DNA damage | [89] |
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Brooks, W. An Epigenetics-Based Hypothesis of Autoantigen Development in Systemic Lupus Erythematosus. Epigenomes 2020, 4, 6. https://doi.org/10.3390/epigenomes4020006
Brooks W. An Epigenetics-Based Hypothesis of Autoantigen Development in Systemic Lupus Erythematosus. Epigenomes. 2020; 4(2):6. https://doi.org/10.3390/epigenomes4020006
Chicago/Turabian StyleBrooks, Wesley. 2020. "An Epigenetics-Based Hypothesis of Autoantigen Development in Systemic Lupus Erythematosus" Epigenomes 4, no. 2: 6. https://doi.org/10.3390/epigenomes4020006