MERVL/Zscan4 Network Activation Results in Transient Genome-wide DNA Demethylation of mESCs
Year: 2016
Type: article
Abstract: Mouse embryonic stem cells are dynamic and heterogeneous. For example, rare cells cycle through a state characterized by decondensed chromatin and expression of transcripts, including the Zscan4 cluster and MERVL endogenous retrovirus, which are usually restricted to preimplantation embryos. Here, we further characterize the dynamics and consequences of this transient cell state. Single-cell transcriptomics identified the earliest upregulated transcripts as cells enter the MERVL/Zscan4 state. The MERVL/Zscan4 transcriptional network was also upregulated during induced pluripotent stem cell reprogramming. Genome-wide DNA methylation and chromatin analyses revealed global DNA hypomethylation accompanying increased chromatin accessibility. This transient DNA demethylation was driven by a loss of DNA methyltransferase proteins in the cells and occurred genome-wide. While methylation levels were restored once cells exit this state, genomic imprints remained hypomethylated, demonstrating a potential global and enduring influence of endogenous retroviral activation on the epigenome.
Source: Cell Reports
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Awards: G1085860639, G1644160072, G2112608321, G2637305634, Adaptation of a high resolution, high throughput assay of immunoglobulin repertoires for commercial and clinical applications, Developmental dynamics of the epigenome, Epigenetic reprogramming in mammalian development., Expanding the potency of stem cells with epigenetic modifiers, G8525317206
OpenAlex ID: W2526632574