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Organization of the Pluripotent Genome.

Authors
  • Lim, Patrick S L1
  • Meshorer, Eran1, 1
  • 1 Department of Genetics, the Institute of Life Sciences; Edmond and Lily Safra Center for Brain Sciences (ELSC), The Hebrew University of Jerusalem, Jerusalem, Israel 9190400. , (Israel)
Type
Published Article
Journal
Cold Spring Harbor Perspectives in Biology
Publisher
Cold Spring Harbor Laboratory
Publication Date
Sep 14, 2020
Identifiers
DOI: 10.1101/cshperspect.a040204
PMID: 32928781
Source
Medline
Language
English
License
Unknown

Abstract

In the past several decades, the establishment of in vitro models of pluripotency has ushered in a golden era for developmental and stem cell biology. Research in this arena has led to profound insights into the regulatory features that shape early embryonic development. Nevertheless, an integrative theory of the epigenetic principles that govern the pluripotent nucleus remains elusive. Here, we summarize the epigenetic characteristics that define the pluripotent state. We cover what is currently known about the epigenome of pluripotent stem cells and reflect on the use of embryonic stem cells as an experimental system. In addition, we highlight insights from super-resolution microscopy, which have advanced our understanding of the form and function of chromatin, particularly its role in establishing the characteristically "open chromatin" of pluripotent nuclei. Further, we discuss the rapid improvements in 3C-based methods, which have given us a means to investigate the 3D spatial organization of the pluripotent genome. This has aided the adaptation of prior notions of a "pluripotent molecular circuitry" into a more holistic model, where hotspots of co-interacting domains correspond with the accumulation of pluripotency-associated factors. Finally, we relate these earlier hypotheses to an emerging model of phase separation, which posits that a biophysical mechanism may presuppose the formation of a pluripotent-state-defining transcriptional program. Copyright © 2020 Cold Spring Harbor Laboratory Press; all rights reserved.

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