Dot1l cooperates with Npm1 to repress endogenous retrovirus MERVL in embryonic stem cells

Dot1l is a histone methyltransferase without a SET domain and is responsible for H3K79 methylation, which marks active transcription. In contradiction, Dot1l also participates in silencing gene expression. The target regions and mechanism of Dot1l in repressing transcription remain enigmatic. Here, we examined the possibility for Dot1l as an repressor of MERVL, which is a marker of 2-cell-like cells. Mechanistically, Dot1l interacted with and colocalized with Npm1 on MERVL, and depletion of Npm1 similarly augmented MERVL expression. We knocked out Dot1l in E14 by CRISPR/Cas9 System. We performed RNA-seq analysis in order to exam the transcriptome after Dot1l KO, performed ChIP-seq analysis in order to exam the DNA binding sites of DOT1L and NPM1.