H3K9 dimethylation safeguards cancer cells against activation of the interferon pathway.

Autor: Hansen AM; The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.; Biotech Research and Innovation Center (BRIC), University of Copenhagen, 2200 Copenhagen, Denmark.; Novo Nordisk Foundation Center for Stem Cell Biology, DanStem, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Ge Y; The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.; Biotech Research and Innovation Center (BRIC), University of Copenhagen, 2200 Copenhagen, Denmark.; Novo Nordisk Foundation Center for Stem Cell Biology, DanStem, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Schuster MB; The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.; Biotech Research and Innovation Center (BRIC), University of Copenhagen, 2200 Copenhagen, Denmark.; Novo Nordisk Foundation Center for Stem Cell Biology, DanStem, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Pundhir S; The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.; Biotech Research and Innovation Center (BRIC), University of Copenhagen, 2200 Copenhagen, Denmark.; Novo Nordisk Foundation Center for Stem Cell Biology, DanStem, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Jakobsen JS; The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.; Biotech Research and Innovation Center (BRIC), University of Copenhagen, 2200 Copenhagen, Denmark.; Novo Nordisk Foundation Center for Stem Cell Biology, DanStem, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Kalvisa A; The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.; Biotech Research and Innovation Center (BRIC), University of Copenhagen, 2200 Copenhagen, Denmark.; Novo Nordisk Foundation Center for Stem Cell Biology, DanStem, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Tapia MC; The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.; Biotech Research and Innovation Center (BRIC), University of Copenhagen, 2200 Copenhagen, Denmark.; Novo Nordisk Foundation Center for Stem Cell Biology, DanStem, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Gordon S; Biotech Research and Innovation Center (BRIC), University of Copenhagen, 2200 Copenhagen, Denmark.; Novo Nordisk Foundation Center for Stem Cell Biology, DanStem, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Ambri F; Biotech Research and Innovation Center (BRIC), University of Copenhagen, 2200 Copenhagen, Denmark.; Novo Nordisk Foundation Center for Stem Cell Biology, DanStem, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Bagger FO; The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.; Biotech Research and Innovation Center (BRIC), University of Copenhagen, 2200 Copenhagen, Denmark.; Novo Nordisk Foundation Center for Stem Cell Biology, DanStem, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.; Center for Genomic Medicine, Copenhagen University Hospital, Copenhagen, Denmark., Pandey D; Biotech Research and Innovation Center (BRIC), University of Copenhagen, 2200 Copenhagen, Denmark.; Department of Microbiology, Oslo University Hospital, NO-0373 Oslo, Norway., Helin K; Biotech Research and Innovation Center (BRIC), University of Copenhagen, 2200 Copenhagen, Denmark.; Novo Nordisk Foundation Center for Stem Cell Biology, DanStem, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.; Cell Biology Program and Center for Epigenetics Research, Memorial Sloan Kettering Center, New York, NY 10065, USA.; The Institute of Cancer Research, London SW3 6JB, United Kingdom., Porse BT; The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.; Biotech Research and Innovation Center (BRIC), University of Copenhagen, 2200 Copenhagen, Denmark.; Novo Nordisk Foundation Center for Stem Cell Biology, DanStem, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2022 Mar 18; Vol. 8 (11), pp. eabf8627. Date of Electronic Publication: 2022 Mar 18.
DOI: 10.1126/sciadv.abf8627
Abstrakt: 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.
Databáze: MEDLINE
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