Widespread Chromatin Accessibility at Repetitive Elements Links Stem Cells with Human Cancer
Open accessAbstract
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.
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References 69 · Cited by 41
- Authors
- Gomez, N. C., Hepperla, A. J., Dumitru, R., Simon, J. M., Fang, F., & Davis, I. J.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Davis, Ian J.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2016-11
- Volume
- 17
- Issue
- 6
- Pages
- 1607-1620
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC5267842
- OpenAlex
- W2548503078
- Cited by
- 41
- References
- 69
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 10 · 2019: 2 · 2018: 12 · 2017: 5
- FWCI
- 3.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UNC Libraries
- Funders
- NIH (R01CA166447, P30CA016086)
- University Cancer Research Fund
- V Foundation for Cancer Research
- Wide Open Foundation
- Corn-Hammond Fund for Pediatric Oncology (T32GM007092)
- Initiative for Maximizing Student Diversity (IMSD) (5R25GM055336)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- chromatin accessibility, repetitive elements, embryonic stem cells, multipotent stem cells, mesenchymal stem cells, nucleosome positioning, histone modifications, chromatin remodeling, cell differentiation, Ewing sarcoma, carcinogenesis, cancer stem cells
- MeSH terms
- Human Embryonic Stem Cells, Base Sequence, Cell Differentiation, Chromatin, Deoxyribonucleases, Histones, Humans, Neoplasms, Nucleosomes, Oncogenes, Protein Processing, Post-Translational, Repetitive Sequences, Nucleic Acid, Stem Cells, Transcription, Genetic, Short Interspersed Nucleotide Elements, Chromatin Assembly and Disassembly
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