Ground State Conditions Induce Rapid Reorganization of Core Pluripotency Factor Binding before Global Epigenetic Reprogramming.

Cell Stem Cell
Authors
Keywords
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.

Year of Publication
2015
Journal
Cell Stem Cell
Volume
17
Issue
4
Pages
462-70
Date Published
2015 Oct 01
ISSN
1875-9777
URL
DOI
10.1016/j.stem.2015.07.005
PubMed ID
26235340
PubMed Central ID
PMC4592414
Links
Grant list
P01 GM099117 / GM / NIGMS NIH HHS / United States
P50 HG006193 / HG / NHGRI NIH HHS / United States
1P50HG006193 / HG / NHGRI NIH HHS / United States
P01GM099117 / GM / NIGMS NIH HHS / United States