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H3K9 dimethylation safeguards cancer cells against activation of the interferon pathway
Activation of interferon genes constitutes an important anticancer pathway able to restrict proliferation of cancer cells. Here, we demonstrate that the H3K9me3 histone methyltransferase (HMT) suppressor of variegation 3–9 homolog 1 (SUV39H1) is required for the proliferation of acute myeloid leukem...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8932663/ https://www.ncbi.nlm.nih.gov/pubmed/35302840 http://dx.doi.org/10.1126/sciadv.abf8627 |
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author | Hansen, Anne Meldgaard Ge, Ying Schuster, Mikkel Bruhn Pundhir, Sachin Jakobsen, Janus Schou Kalvisa, Adrija Tapia, Marta Cecylia Gordon, Sandra Ambri, Francesca Bagger, Frederik Otzen Pandey, Deo Helin, Kristian Porse, Bo Torben |
author_facet | Hansen, Anne Meldgaard Ge, Ying Schuster, Mikkel Bruhn Pundhir, Sachin Jakobsen, Janus Schou Kalvisa, Adrija Tapia, Marta Cecylia Gordon, Sandra Ambri, Francesca Bagger, Frederik Otzen Pandey, Deo Helin, Kristian Porse, Bo Torben |
author_sort | Hansen, Anne Meldgaard |
collection | PubMed |
description | Activation of interferon genes constitutes an important anticancer pathway able to restrict proliferation of cancer cells. Here, we demonstrate that the H3K9me3 histone methyltransferase (HMT) suppressor of variegation 3–9 homolog 1 (SUV39H1) is required for the proliferation of acute myeloid leukemia (AML) and find that its loss leads to activation of the interferon pathway. Mechanistically, we show that this occurs via destabilization of a complex composed of SUV39H1 and the two H3K9me2 HMTs, G9A and GLP. Indeed, loss of H3K9me2 correlated with the activation of key interferon pathway genes, and interference with the activities of G9A/GLP largely phenocopied loss of SUV39H1. Last, we demonstrate that inhibition of G9A/GLP synergized with DNA demethylating agents and that SUV39H1 constitutes a potential biomarker for the response to hypomethylation treatment. Collectively, we uncovered a clinically relevant role for H3K9me2 in safeguarding cancer cells against activation of the interferon pathway. |
format | Online Article Text |
id | pubmed-8932663 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-89326632022-03-31 H3K9 dimethylation safeguards cancer cells against activation of the interferon pathway Hansen, Anne Meldgaard Ge, Ying Schuster, Mikkel Bruhn Pundhir, Sachin Jakobsen, Janus Schou Kalvisa, Adrija Tapia, Marta Cecylia Gordon, Sandra Ambri, Francesca Bagger, Frederik Otzen Pandey, Deo Helin, Kristian Porse, Bo Torben Sci Adv Biomedicine and Life Sciences Activation of interferon genes constitutes an important anticancer pathway able to restrict proliferation of cancer cells. Here, we demonstrate that the H3K9me3 histone methyltransferase (HMT) suppressor of variegation 3–9 homolog 1 (SUV39H1) is required for the proliferation of acute myeloid leukemia (AML) and find that its loss leads to activation of the interferon pathway. Mechanistically, we show that this occurs via destabilization of a complex composed of SUV39H1 and the two H3K9me2 HMTs, G9A and GLP. Indeed, loss of H3K9me2 correlated with the activation of key interferon pathway genes, and interference with the activities of G9A/GLP largely phenocopied loss of SUV39H1. Last, we demonstrate that inhibition of G9A/GLP synergized with DNA demethylating agents and that SUV39H1 constitutes a potential biomarker for the response to hypomethylation treatment. Collectively, we uncovered a clinically relevant role for H3K9me2 in safeguarding cancer cells against activation of the interferon pathway. American Association for the Advancement of Science 2022-03-18 /pmc/articles/PMC8932663/ /pubmed/35302840 http://dx.doi.org/10.1126/sciadv.abf8627 Text en Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Hansen, Anne Meldgaard Ge, Ying Schuster, Mikkel Bruhn Pundhir, Sachin Jakobsen, Janus Schou Kalvisa, Adrija Tapia, Marta Cecylia Gordon, Sandra Ambri, Francesca Bagger, Frederik Otzen Pandey, Deo Helin, Kristian Porse, Bo Torben H3K9 dimethylation safeguards cancer cells against activation of the interferon pathway |
title | H3K9 dimethylation safeguards cancer cells against activation of the interferon pathway |
title_full | H3K9 dimethylation safeguards cancer cells against activation of the interferon pathway |
title_fullStr | H3K9 dimethylation safeguards cancer cells against activation of the interferon pathway |
title_full_unstemmed | H3K9 dimethylation safeguards cancer cells against activation of the interferon pathway |
title_short | H3K9 dimethylation safeguards cancer cells against activation of the interferon pathway |
title_sort | h3k9 dimethylation safeguards cancer cells against activation of the interferon pathway |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8932663/ https://www.ncbi.nlm.nih.gov/pubmed/35302840 http://dx.doi.org/10.1126/sciadv.abf8627 |
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