Inhibitor of growth protein 3 epigenetically silences endogenous retroviral elements and prevents innate immune activation

Abstract Endogenous retroviruses (ERVs) are subject to transcriptional repression in adult tissues, in part to prevent autoimmune responses. However, little is known about the epigenetic silencing of ERV expression. Here, we describe a new role for inhibitor of growth family member 3 (ING3), to add...

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Published inNucleic acids research Vol. 49; no. 22; pp. 12706 - 12715
Main Authors Song, Yanhua, Hou, Gaopeng, Diep, Jonathan, Ooi, Yaw Shin, Akopyants, Natalia S, Beverley, Stephen M, Carette, Jan E, Greenberg, Harry B, Ding, Siyuan
Format Journal Article
LanguageEnglish
Published England Oxford University Press 16.12.2021
Subjects
CRISPR-Cas Systems
Endogenous Retroviruses
Gene regulation, Chromatin and Epigenetics
Gene Silencing
HeLa Cells
Histone Code
Homeodomain Proteins - metabolism
Homeodomain Proteins - physiology
HT29 Cells
Humans
Immunity, Innate - genetics
Tumor Suppressor Proteins - metabolism
Tumor Suppressor Proteins - physiology
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Summary:Abstract Endogenous retroviruses (ERVs) are subject to transcriptional repression in adult tissues, in part to prevent autoimmune responses. However, little is known about the epigenetic silencing of ERV expression. Here, we describe a new role for inhibitor of growth family member 3 (ING3), to add to an emerging group of ERV transcriptional regulators. Our results show that ING3 binds to several ERV promoters (for instance MER21C) and establishes an EZH2-mediated H3K27 trimethylation modification. Loss of ING3 leads to decreases of H3K27 trimethylation enrichment at ERVs, induction of MDA5-MAVS-interferon signaling, and functional inhibition of several virus infections. These data demonstrate an important new function of ING3 in ERV silencing and contributing to innate immune regulation in somatic cells.
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The authors wish it to be known that, in their opinion, the first two authors should be regarded as Joint First Authors.
ISSN:0305-1048
1362-4962
1362-4962
DOI:10.1093/nar/gkab1070