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Epigenetic regulation of open chromatin in pluripotent stem cells

  • Hiroshi Kobayashi
    Affiliations
    Stem Cell Institute, Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN
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  • Nobuaki Kikyo
    Correspondence
    Reprint requests: Nobuaki Kikyo, Stem Cell Institute, University of Minnesota, 2001 6th Street SE, MTRF Room 2-216, Minneapolis, MN 55455
    Affiliations
    Stem Cell Institute, Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN
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Published:March 17, 2014DOI:https://doi.org/10.1016/j.trsl.2014.03.004
      The recent progress in pluripotent stem cell research has opened new avenues of disease modeling, drug screening, and transplantation of patient-specific tissues unimaginable until a decade ago. The central mechanism underlying pluripotency is epigenetic gene regulation; the majority of cell signaling pathways, both extracellular and cytoplasmic, alter, eventually, the epigenetic status of their target genes during the process of activating or suppressing the genes to acquire or maintain pluripotency. It has long been thought that the chromatin of pluripotent stem cells is open globally to enable the timely activation of essentially all genes in the genome during differentiation into multiple lineages. The current article reviews descriptive observations and the epigenetic machinery relevant to what is supposed to be globally open chromatin in pluripotent stem cells, including microscopic appearance, permissive gene transcription, chromatin remodeling complexes, histone modifications, DNA methylation, noncoding RNAs, dynamic movement of chromatin proteins, nucleosome accessibility and positioning, and long-range chromosomal interactions. Detailed analyses of each element, however, have revealed that the globally open chromatin hypothesis is not necessarily supported by some of the critical experimental evidence, such as genomewide nucleosome accessibility and nucleosome positioning. Greater understanding of epigenetic gene regulation is expected to determine the true nature of the so-called globally open chromatin in pluripotent stem cells.

      Abbreviations:

      5hmc (5-hydroxymethylcytosine), 5mC (5-methylcytosine), ATP (adenosine triphosphate), BAF (Brg/Brahma-associated factor), DHS (DNase I hypersensitivity site), ESC (embryonic stem cell), GFP (green fluorescent protein), LOCK (large, organized chromatin K9 modification), iPSC (induced pluripotent stem cell), miRNA (micro-RNA), mRNA (messenger RNA), lncRNA (long noncoding RNA), PRC (polycomb repressive complex), PSC (pluripotent stem cell), SWI/SNF (switching defective/sucrose nonfermenting), Tet (Ten-eleven Translocation)
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