Jüngel, A; Distler, J H W; Gay, S; Distler, O (2011). Epigenetic modifications: novel therapeutic strategies for systemic sclerosis? Expert Review of Clinical Immunology, 7(4):475-480.
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Epigenetic modifications of gene expression comprise modifications of DNA by DNA methylation and modifications of the histone proteins by acetylation, methylation, SUMOylation or phosphorylation. DNA methylation in the promoter region of genes represses gene transcription. Histone modifications influence the structure of DNA and regulate gene expression by changing the availability of DNA for the transcriptional machinery or DNA-binding proteins. Histone modifications are mediated by enzymes and induce or repress gene expression. Aberrant expression of single enzymes disturb the normal balance of these modifiers leading to cancer or autoimmune diseases. We show in this article that epigenetic modifications contribute to the massive production of extracellular matrix proteins in systemic sclerosis skin fibroblasts. Both DNA methylation and histone modifications contribute to the activated phenotype of systemic sclerosis fibroblasts. In vitro and in vivo experiments demonstrate that the use of epigenetic-based drugs on these cells is able to reverse their activated phenotype.
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|Item Type:||Journal Article, refereed, further contribution|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Rheumatology Clinic and Institute of Physical Medicine
04 Faculty of Medicine > Center for Integrative Human Physiology
|DDC:||570 Life sciences; biology
610 Medicine & health
|Deposited On:||06 Jan 2012 14:23|
|Last Modified:||27 Nov 2013 22:07|
|Publisher:||Expert Reviews Ltd.|
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