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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Eckersley-Maslin MA,Svensson V,Krueger C,Stubbs TM,Giehr P,Krueger F,Miragaia RJ,Kyriakopoulos C,Berrens RV,Milagre I,Walter J,Teichmann SA,Reik Wdoi
10.1016/j.celrep.2016.08.087subject
Has Abstractpub_date
2016-09-27 00:00:00pages
179-192issue
1issn
2211-1247pii
S2211-1247(16)31196-2journal_volume
17pub_type
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