Cell Reports Volume 17, Issue 6, p1607–1620, 1 November 2016
Widespread Chromatin Accessibility at Repetitive Elements Links Stem Cells with Human Cancer
Nicholas C. Gomez, Austin J. Hepperla, Raluca Dumitru, Jeremy M. Simon, Fang Fang, Ian J. Davis8, Email the author
• Stem cells are characterized by chromatin accessibility at repetitive elements
• Accessible repetitive elements are marked by distinct histone modifications
• Stem cell differentiation induces chromatin remodeling at repetitive elements
• Stem cell chromatin offers a permissive environment for Ewing sarcoma development
Chromatin regulation is critical for differentiation and disease. However, features linking the chromatin environment of stem cells with disease remain largely unknown. We explored chromatin accessibility in embryonic and multipotent stem cells and unexpectedly identified widespread chromatin accessibility at repetitive elements. Integrating genomic and biochemical approaches, we demonstrate that these sites of increased accessibility are associated with well-positioned nucleosomes marked by distinct histone modifications. Differentiation is accompanied by chromatin remodeling at repetitive elements associated with altered expression of genes in relevant developmental pathways. Remarkably, we found that the chromatin environment of Ewing sarcoma, a mesenchymally derived tumor, is shared with primary mesenchymal stem cells (MSCs). Accessibility at repetitive elements in MSCs offers a permissive environment that is exploited by the critical oncogene responsible for this cancer. Our data demonstrate that stem cells harbor a unique chromatin landscape characterized by accessibility at repetitive elements, a feature associated with differentiation and oncogenesis.
Keywords: stem cell, chromatin, repetitive elements, histone modification, chromatin accessibility, differentiation, Ewing sarcoma, cancer
Received: November 3, 2015; Received in revised form: June 2, 2016; Accepted: October 2, 2016; Published: November 1, 2016
© 2016 The Author(s). Published by Elsevier Inc.
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