MERVL/Zscan4 Network Activation Results in Transient Genome-wide DNA Demethylation of mESCs.


Type
Article
Change log
Authors
Eckersley-Maslin, Mélanie A 
Svensson, Valentine 
Krueger, Christel 
Stubbs, Thomas M 
Giehr, Pascal 
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.

Description
Keywords
DNA methylation, MERVL, Zscan4, chromatin, embryonic stem cell, endogenous retrovirus, imprint, preimplantation, reprogramming, Animals, Cell Cycle, Cellular Reprogramming, Chromatin, DNA Methylation, DNA Modification Methylases, Endogenous Retroviruses, Epigenesis, Genetic, Genome, Genomic Imprinting, Induced Pluripotent Stem Cells, Mice, Mouse Embryonic Stem Cells, Multigene Family, RNA, Messenger, Single-Cell Analysis, Transcription Factors, Transcriptional Activation, Transcriptome
Journal Title
Cell Rep
Conference Name
Journal ISSN
2211-1247
2211-1247
Volume Title
17
Publisher
Elsevier BV