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The Transcriptionaland EpigenomicFoundations of GroundState Pluripotency Hendrik MarksTüzer KalkanRoberta Menafra2012 год

The Transcriptional and Epigenomic Foundations of Ground State Pluripotency
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Аннотация: SummaryMouse 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.Graphical abstractGraphical AbstractHighlights► High-resolution genome-wide transcriptome and epigenome of naive pluripotency ► Reduced H3K27me3 at promoters and fewer bivalent domains in naive ES cells ► Reduced lineage priming and increased RNA polymerase II pausing in the naive state ► Naive ES cells show no delay in differentiation
Год издания: 2012
Авторы: Hendrik Marks, Tüzer Kalkan, Roberta Menafra, Sergey Denissov, Kenneth D. Jones, Helmut Hofemeister, Jennifer Nichols, Andrea Kranz, Aengus Stewart, Austin Smith, Hendrik G. Stunnenberg
Издательство: Cell Press
Источник: Cell
Ключевые слова: Epigenetics and DNA Methylation, Pluripotent Stem Cells Research, CRISPR and Genetic Engineering
Другие ссылки: Cell (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
Radboud Repository (Radboud University) (HTML)
Radboud Repository (Radboud University) (PDF)
Radboud Repository (Radboud University) (HTML)
PubMed (HTML)