Please use this identifier to cite or link to this item: https://doi.org/10.1038/srep28112
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dc.titleHistone modifications and p53 binding poise the p21 promoter for activation in human embryonic stem cells
dc.contributor.authorItahana Y.
dc.contributor.authorZhang J.
dc.contributor.authorGöke J.
dc.contributor.authorVardy L.A.
dc.contributor.authorHan R.
dc.contributor.authorIwamoto K.
dc.contributor.authorCukuroglu E.
dc.contributor.authorRobson P.
dc.contributor.authorPouladi M.A.
dc.contributor.authorColman A.
dc.contributor.authorItahana K.
dc.date.accessioned2020-09-02T06:53:31Z
dc.date.available2020-09-02T06:53:31Z
dc.date.issued2016
dc.identifier.citationItahana Y., Zhang J., Göke J., Vardy L.A., Han R., Iwamoto K., Cukuroglu E., Robson P., Pouladi M.A., Colman A., Itahana K. (2016). Histone modifications and p53 binding poise the p21 promoter for activation in human embryonic stem cells. Scientific Reports 6 : 28112. ScholarBank@NUS Repository. https://doi.org/10.1038/srep28112
dc.identifier.issn20452322
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/174005
dc.description.abstractThe high proliferation rate of embryonic stem cells (ESCs) is thought to arise partly from very low expression of p21. However, how p21 is suppressed in ESCs has been unclear. We found that p53 binds to the p21 promoter in human ESCs (hESCs) as efficiently as in differentiated human mesenchymal stem cells, however it does not promote p21 transcription in hESCs. We observed an enrichment for both the repressive histone H3K27me3 and activating histone H3K4me3 chromatin marks at the p21 locus in hESCs, suggesting it is a suppressed, bivalent domain which overrides activation by p53. Reducing H3K27me3 methylation in hESCs rescued p21 expression, and ectopic expression of p21 in hESCs triggered their differentiation. Further, we uncovered a subset of bivalent promoters bound by p53 in hESCs that are similarly induced upon differentiation in a p53-dependent manner, whereas p53 promotes the transcription of other target genes which do not show an enrichment of H3K27me3 in ESCs. Our studies reveal a unique epigenetic strategy used by ESCs to poise undesired p53 target genes, thus balancing the maintenance of pluripotency in the undifferentiated state with a robust response to differentiation signals, while utilizing p53 activity to maintain genomic stability and homeostasis in ESCs.
dc.sourceUnpaywall 20200831
dc.subjectcyclin dependent kinase inhibitor 1A
dc.subjecthistone
dc.subjectprotein binding
dc.subjectprotein p53
dc.subjectsmall interfering RNA
dc.subjectantagonists and inhibitors
dc.subjectcell differentiation
dc.subjectcell line
dc.subjectcytology
dc.subjectgenetic epigenesis
dc.subjectgenetics
dc.subjecthuman
dc.subjecthuman embryonic stem cell
dc.subjectindirect fluorescent antibody technique
dc.subjectinduced pluripotent stem cell
dc.subjectmetabolism
dc.subjectmethylation
dc.subjectnucleotide sequence
dc.subjectpromoter region
dc.subjectprotein stability
dc.subjectRNA interference
dc.subjecttranscription initiation
dc.subjectBase Sequence
dc.subjectCell Differentiation
dc.subjectCell Line
dc.subjectCyclin-Dependent Kinase Inhibitor p21
dc.subjectEpigenesis, Genetic
dc.subjectFluorescent Antibody Technique, Indirect
dc.subjectHistones
dc.subjectHuman Embryonic Stem Cells
dc.subjectHumans
dc.subjectInduced Pluripotent Stem Cells
dc.subjectMethylation
dc.subjectPromoter Regions, Genetic
dc.subjectProtein Binding
dc.subjectProtein Stability
dc.subjectRNA Interference
dc.subjectRNA, Small Interfering
dc.subjectTranscriptional Activation
dc.subjectTumor Suppressor Protein p53
dc.typeArticle
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.contributor.departmentDEPT OF MEDICINE
dc.description.doi10.1038/srep28112
dc.description.sourcetitleScientific Reports
dc.description.volume6
dc.description.page28112
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