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Cited by 62Epigenetics and DNA MethylationGenomics and Chromatin DynamicsChromatin Remodeling and Cancer

Correlation of DNA methylation with histone modifications across the HNRPA2B1-CBX3 ubiquitously-acting chromatin open element (UCOE)

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Allen, Marianne Lindahl, Antoniou, Michael·2007·Epigenetics
DOI 10.4161/epi.2.4.5231
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Abstract

The methylation-free CpG island encompassing the divergently transcribed promoters of the HNRPA2B1 and CBX3 housekeeping genes possesses a dominant ubiquitously-acting chromatin opening element (UCOE) capability. This element allows reproducible and stable transgene expression including from within centromeric heterochromatin. We present an investigation of DNA methylation and histone modification marks across the HNRPA2B1-CBX3 locus in primary peripheral blood mononuclear cells (PBMCs) to characterise the chromatin structure that underlies UCOE activity. The CpG methylation-free region associated with the UCOE extends into the central areas of HNRPA2B1 and CBX3, with a total length of approximately 5 kb. However, the DNA in the 3' half of both genes is methylated. Histone H4 lysine (K) acetylation shows a broad distribution across both genes, whilst histone H3 lysine acetylation peaks around the transcriptional start sites and drops to background levels at the 3' ends. Higher levels of H3K4 di-methylation are present at the 3' end of the genes in contrast to H3K4 tri-methylation which peaks around the transcriptional start sites. Therefore, methylated DNA in transcribed regions of these genes has been shown here to co-exist with active histone modification marks, indicating that these functionally opposing epigenetic signatures can overlap. This suggests that an extended large region of unmethylated DNA in combination with distinct histone modification patterns are at the basis of UCOE function.

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  • An UCOE can prevent DNA methylation of the CMV promoter region, thus preventing gene expression silencing.

    “It has been shown that an UCOE can also prevent DNA methylation of the CMV promoter region, thus preventing gene expression silencing (Lindahl Allen and Antoniou, 2007;Zhang et al., 2010a).”

    From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Lindahl Allen and Antoniou, 2007

    The Introduction reports that the HNRPA2B1-CBX3 UCOE negates DNA-methylation-mediated silencing of hCMV-promoter-driven transgenes in stably transfected tissue-culture cells. It does not specifically say that the UCOE prevents methylation of the CMV promoter region; the paper’s own methylation analysis concerns the HNRPA2B1-CBX3 locus, not that promoter. (LLM, conf=0.85)

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Cited by

Sorted by citations

Authors
Allen, M. L., & Antoniou, M.
ORCID
Antoniou, Michael
Venue
Epigenetics
Publisher
Informa UK Limited
Published
2007-10-03
Volume
2
Issue
4
Pages
227-236
ISSN
  • 1559-2294 (ISSN-L)
  • 1559-2308
DOI
10.4161/epi.2.4.5231
OpenAlex
W2057407754
Cited by
62
References
1
Citations by year
2025: 4 · 2023: 2 · 2022: 1 · 2020: 1 · 2019: 3 · 2018: 4 · 2017: 8 · 2015: 5 · 2014: 5 · 2013: 7 · 2012: 3
FWCI
1.98
Type
journal article
Language
en
Open access
Locations
  • Epigenetics (publishedVersion)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (submittedVersion)
Funders
Medical Research Council
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 › Molecular Biology › Chromatin Remodeling and Cancer
Keywords
DNA methylation, histone modifications, CBX3, CpG islands, divergent transcription, H3K4 dimethylation, H3K4 trimethylation, centromeric heterochromatin, transgene expression, epigenetic signatures, peripheral blood mononuclear cells
MeSH terms
Acetylation, Cells, Cultured, Chromatin, Chromosomal Proteins, Non-Histone, Histones, Humans, Monocytes, Promoter Regions, Genetic, CpG Islands, DNA Methylation, Reverse Transcriptase Polymerase Chain Reaction, Heterogeneous-Nuclear Ribonucleoprotein Group A-B, Chromatin Immunoprecipitation

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