Genome-wide DNA methylation analysis reveals hypomethylation in the low-CpG promoter regions in lymphoblastoid cell lines
Open accessAbstract
BACKGROUND: Epidemiological studies of DNA methylation profiles may uncover the molecular mechanisms through which genetic and environmental factors contribute to the risk of multifactorial diseases. There are two types of commonly used DNA bioresources, peripheral blood cells (PBCs) and EBV-transformed lymphoblastoid cell lines (LCLs), which are available for genetic epidemiological studies. Therefore, to extend our knowledge of the difference in DNA methylation status between LCLs and PBCs is important in human population studies that use these DNA sources to elucidate the epigenetic risks for multifactorial diseases. We analyzed the methylation status of the autosomes for 192 and 92 DNA samples that were obtained from PBCs and LCLs, respectively, using a human methylation 450 K array. After excluding SNP-associated methylation sites and low-call sites, 400,240 sites were subjected to analysis using a generalized linear model with cell type, sex, and age as the independent variables. RESULTS: We found that the large proportion of sites showed lower methylation levels in LCLs compared with PBCs, which is consistent with previous reports. We also found that significantly different methylation sites tend to be located on the outside of the CpG island and in a region relatively far from the transcription start site. Additionally, we observed that the methylation change of the sites in the low-CpG promoter region was remarkable. Finally, it was shown that the correlation between the chronological age and ageing-associated methylation sites in ELOVL2 and FHL2 in the LCLs was weaker than that in the PBCs. CONCLUSIONS: The methylation levels of highly methylated sites of the low-CpG-density promoters in PBCs decreased in the LCLs, suggesting that the methylation sites located in low-CpG-density promoters could be sensitive to demethylation in LCLs. Despite being generated from a single cell type, LCLs may not always be a proxy for DNA from PBCs in studies of epigenome-wide analysis attempting to elucidate the role of epigenetic change in disease risks.
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CpGs in CG-poor regions are generally methylated, while CpGs within CGIs remain unmethylated in normal cells and aberrantly hypermethylated in cancer.
“The CpGs in CG-poor regions are generally methylated, while CpGs within CGIs remain unmethylated in normal cells49 and aberrantly hypermethylated in cancer2,50.”
From Alternative promoters in CpG depleted regions are prevalently associated with epigenetic misregulation of liver cancer transcriptomes (2023) · cites this paper as [50]
The Results section ('The methylation sites located in low CpG promoters could be sensitive to demethylation in LCLs'; page unavailable) reports that nearly half of low-CpG-promoter sites were highly methylated, while almost all high-CpG-promoter sites were hypomethylated in peripheral blood cells. This supports the claimed contrast, but the paper does not establish it for CG-poor regions and CpG islands generally across normal cells. The cancer clause is attributed to other citations, not this source. (LLM, conf=0.82)
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Nepal, C., & Andersen, J. B. (2023) · Nature Communications · doi:10.1038/s41467-023-38272-4 · Cited by 39 · see citing works
- Authors
- Taniguchi, I., Iwaya, C., Ohnaka, K., Shibata, H., & Yamamoto, K.
- Affiliations
- Kyushu University (JP)
- Kurume University (JP)
- Corresponding author
- Yamamoto, Ken
- Venue
- Human Genomics
- Published
- 2017-05-12
- Volume
- 11
- Issue
- 1
- Pages
- 8-8
- ISSN
- 1473-9542 (ISSN-L)
- 1479-7364
- PMC
- PMC5429538
- OpenAlex
- W2612810442
- Cited by
- 13
- References
- 3
- Citations by year
- 2023: 1 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 1
- FWCI
- 0.45
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Human Genomics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Kyushu University Institutional Repository (QIR) (Kyushu University) (acceptedVersion, other-oa)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- KAKENHI (15K08290)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- DNA methylation, lymphoblastoid cell lines, peripheral blood cells, CpG islands, demethylation, ELOVL2, FHL2, cell type differences, epigenetic biomarkers, genetic epidemiology
- MeSH terms
- Fatty Acid Elongases, Acetyltransferases, Aging, Blood Cells, Cell Line, Transformed, Humans, Lymphocyte Activation, Muscle Proteins, Transcription Factors, CpG Islands, DNA Methylation, Genome-Wide Association Study, LIM-Homeodomain Proteins
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