Abstract：
:Mouse embryonic stem (ES) cells grown in serum exhibit greater heterogeneity in morphology and expression of pluripotency factors than ES cells cultured in defined medium with inhibitors of two kinases (Mek and GSK3), a condition known as "2i" postulated to establish a naive ground state. We show that the transcriptome and epigenome profiles of serum- and 2i-grown ES cells are distinct. 2i-treated cells exhibit lower expression of lineage-affiliated genes, reduced prevalence at promoters of the repressive histone modification H3K27me3, and fewer bivalent domains, which are thought to mark genes poised for either up- or downregulation. Nonetheless, serum- and 2i-grown ES cells have similar differentiation potential. Precocious transcription of developmental genes in 2i is restrained by RNA polymerase II promoter-proximal pausing. These findings suggest that transcriptional potentiation and a permissive chromatin context characterize the ground state and that exit from it may not require a metastable intermediate or multilineage priming.
journal_name
Celljournal_title
Cellauthors
Marks H,Kalkan T,Menafra R,Denissov S,Jones K,Hofemeister H,Nichols J,Kranz A,Stewart AF,Smith A,Stunnenberg HGdoi
10.1016/j.cell.2012.03.026subject
Has Abstractpub_date
2012-04-27 00:00:00pages
590-604issue
3eissn
0092-8674issn
1097-4172pii
S0092-8674(12)00409-6journal_volume
149pub_type
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