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DNA hypomethylation leads to cGAS‐induced autoinflammation in the epidermis
DNA methylation is a fundamental epigenetic modification, important across biological processes. The maintenance methyltransferase DNMT1 is essential for lineage differentiation during development, but its functions in tissue homeostasis are incompletely understood. We show that epidermis‐specific D...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8591534/ https://www.ncbi.nlm.nih.gov/pubmed/34586646 http://dx.doi.org/10.15252/embj.2021108234 |
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author | Beck, Mirjam A Fischer, Heinz Grabner, Lisa M Groffics, Tamara Winter, Mircea Tangermann, Simone Meischel, Tina Zaussinger‐Haas, Barbara Wagner, Patrick Fischer, Carina Folie, Christina Arand, Julia Schöfer, Christian Ramsahoye, Bernard Lagger, Sabine Machat, Georg Eisenwort, Gregor Schneider, Stephanie Podhornik, Alexandra Kothmayer, Michael Reichart, Ursula Glösmann, Martin Tamir, Ido Mildner, Michael Sheibani‐Tezerji, Raheleh Kenner, Lukas Petzelbauer, Peter Egger, Gerda Sibilia, Maria Ablasser, Andrea Seiser, Christian |
author_facet | Beck, Mirjam A Fischer, Heinz Grabner, Lisa M Groffics, Tamara Winter, Mircea Tangermann, Simone Meischel, Tina Zaussinger‐Haas, Barbara Wagner, Patrick Fischer, Carina Folie, Christina Arand, Julia Schöfer, Christian Ramsahoye, Bernard Lagger, Sabine Machat, Georg Eisenwort, Gregor Schneider, Stephanie Podhornik, Alexandra Kothmayer, Michael Reichart, Ursula Glösmann, Martin Tamir, Ido Mildner, Michael Sheibani‐Tezerji, Raheleh Kenner, Lukas Petzelbauer, Peter Egger, Gerda Sibilia, Maria Ablasser, Andrea Seiser, Christian |
author_sort | Beck, Mirjam A |
collection | PubMed |
description | DNA methylation is a fundamental epigenetic modification, important across biological processes. The maintenance methyltransferase DNMT1 is essential for lineage differentiation during development, but its functions in tissue homeostasis are incompletely understood. We show that epidermis‐specific DNMT1 deletion severely disrupts epidermal structure and homeostasis, initiating a massive innate immune response and infiltration of immune cells. Mechanistically, DNA hypomethylation in keratinocytes triggered transposon derepression, mitotic defects, and formation of micronuclei. DNA release into the cytosol of DNMT1‐deficient keratinocytes activated signaling through cGAS and STING, thus triggering inflammation. Our findings show that disruption of a key epigenetic mark directly impacts immune and tissue homeostasis, and potentially impacts our understanding of autoinflammatory diseases and cancer immunotherapy. |
format | Online Article Text |
id | pubmed-8591534 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85915342021-11-26 DNA hypomethylation leads to cGAS‐induced autoinflammation in the epidermis Beck, Mirjam A Fischer, Heinz Grabner, Lisa M Groffics, Tamara Winter, Mircea Tangermann, Simone Meischel, Tina Zaussinger‐Haas, Barbara Wagner, Patrick Fischer, Carina Folie, Christina Arand, Julia Schöfer, Christian Ramsahoye, Bernard Lagger, Sabine Machat, Georg Eisenwort, Gregor Schneider, Stephanie Podhornik, Alexandra Kothmayer, Michael Reichart, Ursula Glösmann, Martin Tamir, Ido Mildner, Michael Sheibani‐Tezerji, Raheleh Kenner, Lukas Petzelbauer, Peter Egger, Gerda Sibilia, Maria Ablasser, Andrea Seiser, Christian EMBO J Articles DNA methylation is a fundamental epigenetic modification, important across biological processes. The maintenance methyltransferase DNMT1 is essential for lineage differentiation during development, but its functions in tissue homeostasis are incompletely understood. We show that epidermis‐specific DNMT1 deletion severely disrupts epidermal structure and homeostasis, initiating a massive innate immune response and infiltration of immune cells. Mechanistically, DNA hypomethylation in keratinocytes triggered transposon derepression, mitotic defects, and formation of micronuclei. DNA release into the cytosol of DNMT1‐deficient keratinocytes activated signaling through cGAS and STING, thus triggering inflammation. Our findings show that disruption of a key epigenetic mark directly impacts immune and tissue homeostasis, and potentially impacts our understanding of autoinflammatory diseases and cancer immunotherapy. John Wiley and Sons Inc. 2021-09-29 2021-11-15 /pmc/articles/PMC8591534/ /pubmed/34586646 http://dx.doi.org/10.15252/embj.2021108234 Text en © 2021 The Authors. Published under the terms of the CC BY 4.0 license https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles Beck, Mirjam A Fischer, Heinz Grabner, Lisa M Groffics, Tamara Winter, Mircea Tangermann, Simone Meischel, Tina Zaussinger‐Haas, Barbara Wagner, Patrick Fischer, Carina Folie, Christina Arand, Julia Schöfer, Christian Ramsahoye, Bernard Lagger, Sabine Machat, Georg Eisenwort, Gregor Schneider, Stephanie Podhornik, Alexandra Kothmayer, Michael Reichart, Ursula Glösmann, Martin Tamir, Ido Mildner, Michael Sheibani‐Tezerji, Raheleh Kenner, Lukas Petzelbauer, Peter Egger, Gerda Sibilia, Maria Ablasser, Andrea Seiser, Christian DNA hypomethylation leads to cGAS‐induced autoinflammation in the epidermis |
title | DNA hypomethylation leads to cGAS‐induced autoinflammation in the epidermis |
title_full | DNA hypomethylation leads to cGAS‐induced autoinflammation in the epidermis |
title_fullStr | DNA hypomethylation leads to cGAS‐induced autoinflammation in the epidermis |
title_full_unstemmed | DNA hypomethylation leads to cGAS‐induced autoinflammation in the epidermis |
title_short | DNA hypomethylation leads to cGAS‐induced autoinflammation in the epidermis |
title_sort | dna hypomethylation leads to cgas‐induced autoinflammation in the epidermis |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8591534/ https://www.ncbi.nlm.nih.gov/pubmed/34586646 http://dx.doi.org/10.15252/embj.2021108234 |
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