Pluto Bioinformatics

GSE75751: Chromatin decompaction coupled MuERVL endogenous retrovirus activation induces genome-wide DNA demethylation

Bulk RNA sequencing

Mouse embryonic stem cells are heterogeneous and contain rare cells expressing transcripts normally upregulated in pre-implantation embryos, including the Zscan4 cluster and MuERVL endogenous retrovirus. Through single cell transcriptomics and genome-wide chromatin and DNA methylation analyses we uncover the dynamics of the regulation and epigenetic consequences of these transient cells. Transcriptional activation of MuERVL and Zscan4 coincided with a global increase in chromatin accessibility. Through a combination of bulk and single-cell RNA-sequencing, we reveal the dynamics and specificities of a MuERVL driven transcriptional network. Interestingly, in addition to pre-implantation embryos, the MuERVL network is similarly upregulated during somatic cell reprogramming, associating it with dramatic chromatin remodeling events. In MuERVL+ mESCs, upregulation of a cluster of Eif1A-like genes results in inhibition of protein synthesis, uncoupling transcription from translation. Consequently, depletion of proteins including DNA methyltransferases, results in genome-wide DNA demethylation, demonstrating the influence of endogenous retroviral activation on the host epigenome. SOURCE: Felix Krueger (felix.krueger@babraham.ac.uk) - The Babraham Institute