TRIM28 controls a gene regulatory network based on endogenous retroviruses in human neural progenitor cells

Endogenous retroviruses (ERVs), which make up 8% of the human genome, have been proposed to participate in the control of gene regulatory networks. In this study, we find a region- and developmental stage-specific expression pattern of ERVs in the developing human brain, which is linked to a transcriptional network based on ERVs. We demonstrate that almost ten thousand, primarily primate-specific ERVs, act as docking platforms for the epigenetic co-repressor protein TRIM28 in human neural progenitor cells, which results in the establishment of local heterochromatin. Thereby, TRIM28 represses ERVs and consequently regulates the expression of neighboring genes. These results uncover a gene regulatory network based on ERVs that participates in control of gene expression of protein-coding transcripts important for brain development. Overall design: ChIP-seq; TRIM28 and H3K9me3 in hNPCs, normalized to total input. RNA-seq; WT and TRIM28-KD two hNPCs cell lines. One fetal derived (Sai2) and one iPS-derived (AF22) , three replicates each treatment and each cell line. RNA-seq of the fetal brain.