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Brooks WH, Renaudineau Y. Epigenetics and autoimmune diseases: the X chromosome-nucleolus nexus. Front Genet. 2015;6:22doi: 10.3389/fgene.2015.00022.
Brooks, W. H., & Renaudineau, Y. (2015). Epigenetics and autoimmune diseases: the X chromosome-nucleolus nexus. Frontiers in genetics, 622. https://doi.org/10.3389/fgene.2015.00022
Brooks, Wesley H, and Renaudineau, Yves. "Epigenetics and autoimmune diseases: the X chromosome-nucleolus nexus." Frontiers in genetics vol. 6 (2015): 22. doi: https://doi.org/10.3389/fgene.2015.00022
Brooks WH, Renaudineau Y. Epigenetics and autoimmune diseases: the X chromosome-nucleolus nexus. Front Genet. 2015 Feb 16;6:22. doi: 10.3389/fgene.2015.00022. eCollection 2015. PMID: 25763008; PMCID: PMC4329817.
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Front Genet. 2015 Feb 16;6:22. doi: 10.3389/fgene.2015.00022. eCollection 2015.

Epigenetics and autoimmune diseases: the X chromosome-nucleolus nexus.

Frontiers in genetics

Wesley H Brooks, Yves Renaudineau

Affiliations

  1. Department of Chemistry, University of South Florida Tampa, FL, USA.
  2. Research Unit INSERM ERI29/EA2216, SFR ScinBios, Labex Igo "Immunotherapy Graft, Oncology", Réseau Épigénétique et Réseau Canaux Ioniques du Cancéropole Grand Ouest, European University of Brittany Brest, France ; Laboratory of Immunology and Immunotherapy, Hôpital Morvan Brest, France.

PMID: 25763008 PMCID: PMC4329817 DOI: 10.3389/fgene.2015.00022

Abstract

Autoimmune diseases occur more often in females, suggesting a key role for the X chromosome. X chromosome inactivation, a major epigenetic feature in female cells that provides dosage compensation of X-linked genes to avoid overexpression, presents special vulnerabilities that can contribute to the disease process. Disruption of X inactivation can result in loss of dosage compensation with expression from previously sequestered genes, imbalance of gene products, and altered endogenous material out of normal epigenetic context. In addition, the human X has significant differences compared to other species and these differences can contribute to the frequency and intensity of the autoimmune disease in humans as well as the types of autoantigens encountered. Here a link is demonstrated between autoimmune diseases, such as systemic lupus erythematosus, and the X chromosome by discussing cases in which typically non-autoimmune disorders complicated with X chromosome abnormalities also present lupus-like symptoms. The discussion is then extended to the reported spatial and temporal associations of the inactive X chromosome with the nucleolus. When frequent episodes of cellular stress occur, the inactive X chromosome may be disrupted and inadvertently become involved in the nucleolar stress response. Development of autoantigens, many of which are at least transiently components of the nucleolus, is then described. Polyamines, which aid in nucleoprotein complex assembly in the nucleolus, increase further during cell stress, and appear to have an important role in the autoimmune disease process. Autoantigenic endogenous material can potentially be stabilized by polyamines. This presents a new paradigm for autoimmune diseases: that many are antigen-driven and the autoantigens originate from altered endogenous material due to episodes of cellular stress that disrupt epigenetic control. This suggests that epigenetics and the X chromosome are important aspects of autoimmune diseases.

Keywords: Alu; NETosis; X chromosome; autoimmune disease; epigenetics; lupus; nucleolus; polyamines

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