Premium
Activation of endogenous retroviruses during brain development causes an inflammatory response
Author(s) -
Jönsson Marie E,
Garza Raquel,
Sharma Yogita,
Petri Rebecca,
Södersten Erik,
Johansson Jenny G,
Johansson Pia A,
Atacho Diahann AM,
Pircs Karolina,
Madsen Sofia,
Yudovich David,
Ramakrishnan Ramprasad,
Holmberg Johan,
Larsson Jonas,
Jern Patric,
Jakobsson Johan
Publication year - 2021
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2020106423
Subject(s) - biology , endogenous retrovirus , epigenetics , gene silencing , microglia , neurogenesis , repressor , regulation of gene expression , gene , genetics , gene expression , neuroscience , inflammation , genome , immunology
Endogenous retroviruses (ERVs) make up a large fraction of mammalian genomes and are thought to contribute to human disease, including brain disorders. In the brain, aberrant activation of ERVs is a potential trigger for an inflammatory response, but mechanistic insight into this phenomenon remains lacking. Using CRISPR/Cas9‐based gene disruption of the epigenetic co‐repressor protein Trim28, we found a dynamic H3K9me3‐dependent regulation of ERVs in proliferating neural progenitor cells (NPCs), but not in adult neurons. In vivo deletion of Trim28 in cortical NPCs during mouse brain development resulted in viable offspring expressing high levels of ERVs in excitatory neurons in the adult brain. Neuronal ERV expression was linked to activated microglia and the presence of ERV‐derived proteins in aggregate‐like structures. This study demonstrates that brain development is a critical period for the silencing of ERVs and provides causal in vivo evidence demonstrating that transcriptional activation of ERV in neurons results in an inflammatory response.