The transcriptional and epigenomic foundations of ground state pluripotency

Cell
Hendrik MarksHendrik G Stunnenberg

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.

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Datasets Mentioned

BETA
GSE23943

Methods Mentioned

BETA
RNA-seq
flow cytometry
immunoprecipitation
ChIP-seq
PCR
immunoprecipitations
ChIP

Related Concepts

Metazoa
Cell Differentiation Process
Histone H7
Methylation
RNA Polymerase II
Transcription, Genetic
v-myc Oncogenes
Histone Code
Epigenesis, Genetic
Mouse, Swiss

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