Abstract：
:Mouse embryonic stem cells (mESCs) cultured under serum/LIF conditions exhibit heterogeneous expression of pluripotency-associated factors that can be overcome by two inhibitors (2i) of the MEK and GSK3 pathways. Several studies have shown that the "ground state" induced by 2i is characterized by global hypomethylation and specific transcriptional profiles, but little is known about the contributing effectors. Here we show that 2i conditions rapidly alter the global binding landscape of OCT4, SOX2, and NANOG. The dynamic binding influences enhancer activity and shows enrichment for regulators linked to Wnt and Erk signaling. Epigenomic characterization provided limited insights to the immediate transcriptional dynamics, suggesting that these are likely more secondary effects. Likewise, loss of the PRC2 component EED to prevent H3K27me3 deposition had minimal effect on the transcriptome, implying that it is largely dispensable for continued repression of bivalent genes and de novo silencing in 2i.
journal_name
Cell Stem Celljournal_title
Cell stem cellauthors
Galonska C,Ziller MJ,Karnik R,Meissner Adoi
10.1016/j.stem.2015.07.005subject
Has Abstractpub_date
2015-10-01 00:00:00pages
462-70issue
4eissn
1934-5909issn
1875-9777pii
S1934-5909(15)00304-5journal_volume
17pub_type
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