TRIM28 Represses Transcription of Endogenous Retroviruses in Neural Progenitor Cells

•Deletion of TRIM28 in NPCs results in transcriptional activation of ERVs•ERVs are marked by H3K9me3 in NPCs, which is lost upon TRIM28 deletion•Activation of ERVs in NPCs influences expression levels of nearby genes•Activation of ERVs in NPCs results in the production of long noncoding RNAs

SummaryTRIM28 is a corepressor that mediates transcriptional silencing by establishing local heterochromatin. Here, we show that deletion of TRIM28 in neural progenitor cells (NPCs) results in high-level expression of two groups of endogenous retroviruses (ERVs): IAP1 and MMERVK10C. We find that NPCs use TRIM28-mediated histone modifications to dynamically regulate transcription and silencing of ERVs, which is in contrast to other somatic cell types using DNA methylation. We also show that derepression of ERVs influences transcriptional dynamics in NPCs through the activation of nearby genes and the expression of long noncoding RNAs. These findings demonstrate a unique dynamic transcriptional regulation of ERVs in NPCs. Our results warrant future studies on the role of ERVs in the healthy and diseased brain.

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