Genome-wide multi-layered epigenomic profiling across human aging
bioRxiv (Cold Spring Harbor Laboratory)
Abstract
Abstract Aging is characterized by highly reproducible alterations across multiple layers of the epigenetic landscape, including DNA methylation, chromatin accessibility, and histone modifications. However, it remains unclear to what extent these age-associated changes are interconnected and coordinated coherently. To investigate the genome-wide distribution and interplay of age-associated epigenetic alterations, we generated whole-genome bisulfite sequencing (WGBS) data from blood samples of 120 healthy donors. Integration with ATAC-seq data revealed no clear relationship between age-related changes in DNA methylation and chromatin accessibility. We further examined the association of these alterations with age-dependent changes in CTCF occupancy and histone modifications, including H3K27ac, H3K27me3, H3K4me1, H3K4me3, and H3K9me3, but observed very little corresponding changes in chromatin states. Collectively, our integrative genome-wide analysis revealed only limited association between age-associated epigenetic alterations in DNA methylation, chromatin accessibility, and histone modifications, arguing against a broadly coordinated remodeling of the aging epigenome.
Authors 10
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Hasso Plattner Institute · University of Potsdam · Max Planck Institute for Molecular Genetics
Affiliation as printed
Digital Engineering Faculty, Hasso Plattner Institute for Digital Engineering, University of Potsdam, Potsdam, Germany
Max Planck Institute for Molecular Genetics, Berlin, Germany
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Affiliation as printed
Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University Medical School, 52074 Aachen, Germany
Institute for Stem Cell Biology, RWTH Aachen University Medical School, 52074 Aachen, Germany
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Affiliation as printed
Center for Computational Life Sciences, RWTH Aachen University, Aachen, Germany
Institute for Computational Genomics, RWTH Aachen University, Medical Faculty, Aachen, Germany
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Affiliation as printed
Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University Medical School, 52074 Aachen, Germany
Institute for Stem Cell Biology, RWTH Aachen University Medical School, 52074 Aachen, Germany
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Affiliation as printed
Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University Medical School, 52074 Aachen, Germany
Institute for Stem Cell Biology, RWTH Aachen University Medical School, 52074 Aachen, Germany
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Institute for Transfusion Medicine and Cell Therapy, University Hospital of RWTH Aachen, Aachen, Germany
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Max Planck Institute for Molecular Genetics · Freie Universität Berlin
Affiliation as printed
Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany
Max Planck Institute for Molecular Genetics, Berlin, Germany
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Affiliation as printed
Center for Computational Life Sciences, RWTH Aachen University, Aachen, Germany
Institute for Computational Genomics, RWTH Aachen University, Medical Faculty, Aachen, Germany
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Hasso Plattner Institute · University of Potsdam · Max Planck Institute for Molecular Genetics
Affiliation as printed
Digital Engineering Faculty, Hasso Plattner Institute for Digital Engineering, University of Potsdam, Potsdam, Germany
Max Planck Institute for Molecular Genetics, Berlin, Germany
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Affiliation as printed
Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University Medical School, 52074 Aachen, Germany
Institute for Stem Cell Biology, RWTH Aachen University Medical School, 52074 Aachen, Germany
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