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Locus- and cell type-specific epigenetic switching during cellular differentiation in mammals

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Frontiers in Biology

Abstract

Background

Epigenomic reconfiguration, including changes in DNA methylation and histone modifications, is crucial for the differentiation of embryonic stem cells (ESCs) into somatic cells. However, the extent to which the epigenome is reconfigured and the interplay between components of the epigenome during cellular differentiation remain poorly defined.

Methods

We systematically analyzed and compared DNA methylation, various histone modification, and transcriptome profiles in ESCs with those of two distinct types of somatic cells from human and mouse.

Results

We found that global DNA methylation levels are lower in somatic cells compared to ESCs in both species. We also found that 80% of regions with histone modification occupancy differ between human ESCs and the two human somatic cell types. Approximately 70% of the reconfigurations in DNA methylation and histone modifications are locus- and cell typespecific. Intriguingly, the loss of DNA methylation is accompanied by the gain of different histone modifications in a locus- and cell type-specific manner. Further examination of transcriptional changes associated with epigenetic reconfiguration at promoter regions revealed an epigenetic switching for gene regulation—a transition from stable gene silencing mediated by DNA methylation in ESCs to flexible gene repression facilitated by repressive histone modifications in somatic cells.

Conclusions

Our findings demonstrate that the epigenome is reconfigured in a locus- and cell type-specific manner and epigenetic switching is common during cellular differentiation in both human and mouse.

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Authors and Affiliations

  1. Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA

    Ying-Tao Zhao, Maria Fasolino & Zhaolan Zhou

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  1. Ying-Tao Zhao
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  2. Maria Fasolino
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  3. Zhaolan Zhou
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Correspondence to Zhaolan Zhou.

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Zhao, YT., Fasolino, M. & Zhou, Z. Locus- and cell type-specific epigenetic switching during cellular differentiation in mammals. Front. Biol. 11, 311–322 (2016). https://doi.org/10.1007/s11515-016-1411-5

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