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Review
. 2011 Jan;10(1):37-49.
doi: 10.1093/bfgp/elq038.

Chromatin structure of pluripotent stem cells and induced pluripotent stem cells

Paul Delgado-Olguín  1 , Félix Recillas-Targa
Affiliations
Review

Chromatin structure of pluripotent stem cells and induced pluripotent stem cells

Paul Delgado-Olguín et al. Brief Funct Genomics. 2011 Jan.

Abstract

Pluripotent embryonic stem (ES) cells are specialized cells with a dynamic chromatin structure, which is intimately connected with their pluripotency and physiology. In recent years somatic cells have been reprogrammed to a pluripotent state through over-expression of a defined set of transcription factors. These cells, known as induced pluripotent stem (iPS) cells, recapitulate ES cell properties and can be differentiated to apparently all cell lineages, making iPS cells a suitable replacement for ES cells in future regenerative medicine. Chromatin modifiers play a key function in establishing and maintaining pluripotency, therefore, elucidating the mechanisms controlling chromatin structure in both ES and iPS cells is of utmost importance to understanding their properties and harnessing their therapeutic potential. In this review, we discuss recent studies that provide a genome-wide view of the chromatin structure signature in ES cells and iPS cells and that highlight the central role of histone modifiers and chromatin remodelers in pluripotency maintenance and induction.

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Figures

Figure 1:
Figure 1:
Model of chromatin reorganization in pluripotency induction. Histone and DNA modifiers participate in the establishment of a generally relaxed and plastic chromatin structure needed for pluripotency induction and maintenance. On the other hand, these epigenetic regulators also control gene expression programs determining cell fate and regulating differentiation. Upon cell reprogramming by OSKM induction, ES cell-differentiated cell fusion or nuclear reprogramming, the pluripotency-associated genes transition from an inactive to an active stage. In differentiated cells, pluripotency regulators are kept repressed by the action of the PcG of proteins via the histone methyltransferase Ezh2, which catalyzes H3K27me3 and G9a, which catalyzes H3K9me3. Additionally, gene repression is ensured by heavy DNA methylation. Upon pluripotency induction, H3K27me3 and H3K9me3 are removed likely by the histone methyltransferases Jmjd3 and Utx and by Jmjd2c and Jmjd1a, respectively, while DNA methylations are removed by AID. Simultaneously, members of the Trx group of proteins introduce H3K4me3, while P300/CBP acetylates histones and ATP-dependent chromatin remodelers of the BAF complex shift nucleosomes, promoting establishment of transcriptionally permissive chromatin and gene expression activation (curved arrow). Differentiation regulators, actively expressed in differentiated cells, are poorly methylated and have a permissive chromatin structure favored by enzymes mediating H3K4me3, histone acetylation and ATP-dependent chromatin remodelers. Upon pluripotency induction, the differentiation regulators shift to a chromatin configuration characterized by the presence of the bivalent marks H3K27me3 and H3K4me3. This chromatin configuration allows for basal gene expression (small curved arrow), while poising genes for repression or activation in future cell fate decisions. Additionally, establishment of DNA demethylation windows poises differentiation regulators for gene activation during cell differentiation. Telomeres are heavily methylated and enriched in repressive histone marks H3K9me3 and H4K20me3, which are catalyzed by Suv4-20h1 and 2. Upon pluripotency induction, telomere length increases along with decreased histone and DNA methylation levels. Whether H3K9 and H4K20 demethylases participate in telomere remodeling is not known.
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