Distinct Epigenomic Landscapes of Pluripotent and Lineage-committed Human Cells

By R. D. Hawkins, Gary Chung Hon, Leonard K. Lee, Queminh Ngo, Ryan Lister, Mattia Pelizzola, Lee E. Edsall, Samantha Kuan, Ying Luu, Sarit A. Klugman and 11 more. Cell Stem Cell, 2010

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SUMMARY Human embryonic stem cells (hESCs) share an identical genome with lineage-committed cells, yet possess the remarkable properties of self-renewal and pluripotency. The diverse cellular properties in different cells have been attributed to their distinct epigenomes, but how much epigenomes differ remains unclear. Here, we report that epigenomic landscapes in hESC and lineage committed cells are drastically different. By comparing the chromatin modification profiles and DNA methylomes in hESCs and primary fibroblasts, we find that nearly one-third of the genome differs in chromatin structure. Most changes arise from dramatic redistributions of repressive H3K9me3 and H3K27me3 marks, which form blocks that significantly expand in fibroblasts. A large number of potential regulatory sequences also exhibit a high degree of dynamics in chromatin modifications and DNA methylation. Additionally, we observe novel, context-dependent relationships between DNA methylation and chromatin modifications. Our results provide new insights into epigenetic mechanisms underlying properties of pluripotency and cell-fate commitment.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/31af77f977d4e37f9ce31eb26bc36b260e46f9f6

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Citations in the corpus

Epithelial-mesenchymal plasticity in cancer progression and metastasis (2019, background): “Reprogramming of the genome-scale epigenetic landscape occurs during normal development and differentiation and contributes to pathological EMT (Hawkins et al., 2010; McDonald et al., 2011).”
Genome-wide mapping of nucleosome positioning and DNA methylation within individual DNA molecules (2012, methodology): “www.genome.org with a H3K4me1+/H3K4me3 profile were taken from Supplemental Table 12 (mmc11.xls) of the same reference (Hawkins et al. 2010; GEO ID GSE16256).”
Systematic mapping of occluded genes by cell fusion reveals prevalence and stability of cis-mediated silencing in somatic cells (2014, methodology): “For all histone marks except H3K9me3 and H3K27me3, chromatin precipitation was performed following the published protocol (Hawkins et al. 2010) with the following modifications: Approximately 10(8) 129TF cells were fixed in 1% formaldehyde for 10 min at room temperature, and sonicated on ice using a”
Reference Maps of Human ES and iPS Cell Variation Enable High-Throughput Characterization of Pluripotent Cell Lines (2011, positive): “Previous research has shown that human pluripotent cells exhibit highly characteristic patterns of DNAmethylation and gene expression (Guenther et al., 2010; Hawkins et al., 2010; Lister et al., 2009; Müller et al., 2008).”
Charting histone modifications and the functional organization of mammalian genomes (2011, background): “At many loci, differentiation is also accompanied by dramatic spreading of the histone modification to yield contiguous but more diffuse domains of H3K27me3 (Ref”
Energy Metabolism in Human Pluripotent Stem Cells and Their Differentiated Counterparts (2011, neutral): “cell types are not identical [4,5,6,7,8].”
Cancer Genetics and Epigenetics: Two Sides of the Same Coin? (2012, background): “While non-CpG methylation has been reported in pluripotent cells (Hawkins et al., 2010; Meissner et al., 2008), DNA methylation in mammals occurs predominantly at CpG dinucleotides, and methylation of CpG islands acts as a relatively stable gene silencing mechanism (Jones and Liang, 2009).”