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Cited by 115Epigenetics and DNA MethylationGenomics and Chromatin DynamicsGenetic Syndromes and Imprinting

A comprehensive analysis of 195 DNA methylomes reveals shared and cell-specific features of partially methylated domains

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DEEP Consortium, Salhab, Abdulrahman, Nordström, Karl, Gasparoni, Gilles, Kattler, Kathrin, Ebert, Peter, Ramirez, Fidel, Arrigoni, Laura +7 more·2018·Genome Biology
DOI 10.1186/s13059-018-1510-5PMC PMC6161375

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Abstract

BACKGROUND: Partially methylated domains are extended regions in the genome exhibiting a reduced average DNA methylation level. They cover gene-poor and transcriptionally inactive regions and tend to be heterochromatic. We present a comprehensive comparative analysis of partially methylated domains in human and mouse cells, to identify structural and functional features associated with them. RESULTS: Partially methylated domains are present in up to 75% of the genome in human and mouse cells irrespective of their tissue or cell origin. Each cell type has a distinct set of partially methylated domains, and genes expressed in such domains show a strong cell type effect. The methylation level varies between cell types with a more pronounced effect in differentiating and replicating cells. The lowest level of methylation is observed in highly proliferating and immortal cancer cell lines. A decrease of DNA methylation within partially methylated domains tends to be linked to an increase in heterochromatic histone marks and a decrease of gene expression. Characteristic combinations of heterochromatic signatures in partially methylated domains are linked to domains of early and middle S-phase and late S-G2 phases of DNA replication. CONCLUSIONS: Partially methylated domains are prominent signatures of long-range epigenomic organization. Integrative analysis identifies them as important general, lineage- and cell type-specific topological features. Changes in partially methylated domains are hallmarks of cell differentiation, with decreased methylation levels and increased heterochromatic marks being linked to enhanced cell proliferation. In combination with broad histone marks, partially methylated domains demarcate distinct domains of late DNA replication.

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Authors
DEEP Consortium, Salhab, A., Nordström, K., Gasparoni, G., Kattler, K., Ebert, P., Ramirez, F., Arrigoni, L., Müller, F., Polansky, J. K., Cadenas, C., G.Hengstler, J., Lengauer, T., Manke, T., & Walter, J.
Affiliations
  • Saarland University (DE)
  • Max Planck Institute for Informatics (DE)
  • Max Planck Institute of Immunobiology and Epigenetics (DE)
  • German Rheumatism Research Centre (DE)
  • Leibniz Research Centre for Working Environment and Human Factors (DE)
Corresponding author
Walter, Jörn
ORCID
Venue
Genome Biology
Publisher
Springer Science and Business Media LLC
Published
2018-09-28
Volume
19
Issue
1
Pages
150-150
ISSN
  • 1465-6906 (ISSN-L)
  • 1474-760X
DOI
10.1186/s13059-018-1510-5
PMC
PMC6161375
OpenAlex
W2894501644
Cited by
115
References
6
Citations by year
2026: 5 · 2025: 9 · 2024: 11 · 2023: 27 · 2022: 12 · 2021: 25 · 2020: 13 · 2019: 12 · 2018: 1
FWCI
5.34
Type
journal article
Language
en
Open access
Licence
Locations
  • Genome biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Funders
  • DEEP (01KU1216F)
  • BLUEPRINT (282510)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
Keywords
partially methylated domains, DNA methylation, heterochromatin, histone modifications, cell type-specific methylation, cell differentiation, cell proliferation, DNA replication timing, S phase, gene expression, cancer cell lines
MeSH terms
Animals, Cell Line, DNA Replication, Heterochromatin, Humans, Neoplasms, Organ Specificity, Transcription, Genetic, Genome, Human, DNA Methylation, Mice

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