Loss of H3K9me3 maintenance leads in human neural progenitor cells leads to transcriptional activation of L1 retrotransposons [Bulk RNA-seq]

We used CRISPRi-mediated deletion of the H3K9me3 methyltransferase SETDB1 in a human neural epithelial-like stem cell line with the characteristics of human neural progenitor cells (hNPCs) to model disruption of heterochromatin maintenance. We found that a key event following the loss of H3K9me3 maintenance was the expression of evolutionary young full-length L1 elements. Transcriptional activation of L1s was associated with a loss of CpG DNA methylation at their promoters, suggesting that deposition of H3K9me3 at the L1 promoter is required to maintain DNA methylation. Overall design: Expression levels of genes and transposable elements in human neural pluripotent stem cells (hNPCs) was examined by Bulk-RNA sequencing in two different conditions: LacZ - CRISPRi (a control targetting a bacterial gene which is not present in the human genome) and SETDB1 - CRISPRi.