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

Yanhua Song, Gaopeng Hou, Jonathan Diep, Yaw Shin Ooi, Natalia S. Akopyants, Stephen M. Beverley, Jan E. Carette, Harry B. Greenberg, Siyuan Ding

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)12706-12715
Number of pages10
JournalNucleic acids research
Volume49
Issue number22
DOIs
StatePublished - Dec 16 2021

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