TY - JOUR
T1 - Inhibitor of growth protein 3 epigenetically silences endogenous retroviral elements and prevents innate immune activation
AU - Song, Yanhua
AU - Hou, Gaopeng
AU - Diep, Jonathan
AU - Ooi, Yaw Shin
AU - Akopyants, Natalia S.
AU - Beverley, Stephen M.
AU - Carette, Jan E.
AU - Greenberg, Harry B.
AU - Ding, Siyuan
N1 - Publisher Copyright:
© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.
PY - 2021/12/16
Y1 - 2021/12/16
N2 - 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-MAVSinterferon 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.
AB - 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-MAVSinterferon 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.
UR - http://www.scopus.com/inward/record.url?scp=85122843129&partnerID=8YFLogxK
U2 - 10.1093/nar/gkab1070
DO - 10.1093/nar/gkab1070
M3 - Article
C2 - 34791430
AN - SCOPUS:85122843129
SN - 0305-1048
VL - 49
SP - 12706
EP - 12715
JO - Nucleic acids research
JF - Nucleic acids research
IS - 22
ER -