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Cited by 547Genomics and Chromatin DynamicsEpigenetics and DNA MethylationCancer-related gene regulation

Dynamic histone H3 methylation during gene induction: HYPB/Setd2 mediates all H3K36 trimethylation

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Edmunds, John W, Mahadevan, Louis C, Clayton, Alison L·2008·The EMBO Journal
DOI 10.1038/sj.emboj.7601967PMC PMC2168397
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Abstract

Understanding the function of histone modifications across inducible genes in mammalian cells requires quantitative, comparative analysis of their fate during gene activation and identification of enzymes responsible. We produced high-resolution comparative maps of the distribution and dynamics of H3K4me3, H3K36me3, H3K79me2 and H3K9ac across c-fos and c-jun upon gene induction in murine fibroblasts. In unstimulated cells, continuous turnover of H3K9 acetylation occurs on all K4-trimethylated histone H3 tails; distribution of both modifications coincides across promoter and 5' part of the coding region. In contrast, K36- and K79-methylated H3 tails, which are not dynamically acetylated, are restricted to the coding regions of these genes. Upon stimulation, transcription-dependent increases in H3K4 and H3K36 trimethylation are seen across coding regions, peaking at 5' and 3' ends, respectively. Addressing molecular mechanisms involved, we find that Huntingtin-interacting protein HYPB/Setd2 is responsible for virtually all global and transcription-dependent H3K36 trimethylation, but not H3K36-mono- or dimethylation, in these cells. These studies reveal four distinct layers of histone modification across inducible mammalian genes and show that HYPB/Setd2 is responsible for H3K36 trimethylation throughout the mouse nucleus.

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  • SETD2 deposits H3K36me3 after Pol2 passage, which in turn recruits DNMT3B to maintain a repressive chromatin state.

    “The methyltransferase SETD2 deposits H3K36me355 after Pol2 passage56, which in turn recruits DNMT3B21 to maintain a repressive chromatin state57.”

    From Alternative promoters in CpG depleted regions are prevalently associated with epigenetic misregulation of liver cancer transcriptomes (2023) · cites this paper as [56]

    The Results section ('Setd2 is non-redundantly responsible for H3K36 trimethylation in mouse fibroblasts'; page unavailable) identifies Setd2 as necessary for virtually all H3K36 trimethylation. The Discussion ('Setd2 mediates H3K36 trimethylation at the 3′ end of active gene coding regions'; page unavailable) suggests that SETD2 may travel with Pol II and methylate K36 co-transcriptionally, but does not establish deposition specifically after Pol II passage. The DNMT3B clause has separate citations in the printed sentence and is not attributed to this source. (LLM, conf=0.85)

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Cited by

Sorted by citations

Authors
Edmunds, J. W., Mahadevan, L. C., & Clayton, A. L.
Affiliations
University of Oxford (GB)
Corresponding author
Mahadevan, Louis C
Venue
The EMBO Journal
Publisher
Springer Science and Business Media LLC
Published
2007-12-20
Volume
27
Issue
2
Pages
406-420
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
DOI
10.1038/sj.emboj.7601967
PMC
PMC2168397
OpenAlex
W2130109827
Cited by
547
References
4
Citations by year
2026: 23 · 2025: 38 · 2024: 24 · 2023: 40 · 2022: 40 · 2021: 40 · 2020: 33 · 2019: 23 · 2018: 29 · 2017: 33 · 2016: 39 · 2015: 34 · 2014: 37 · 2013: 25 · 2012: 22
FWCI
6.50
Type
journal article
Language
en
Open access
Licence
Locations
  • The EMBO Journal (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • University of Portsmouth
  • Wellcome Trust (065373)
  • Medical Research Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
Keywords
histone H3 methylation, H3K36 trimethylation, H3K4me3, H3K79me2, H3K9 acetylation, gene induction, c-fos, c-Jun, transcriptional activation, inducible genes, mouse fibroblasts
MeSH terms
Animals, Cell Line, Epidermal Growth Factor, Gene Expression Regulation, Histones, Lysine, Methylation, Mice, Inbred C3H, Transcription, Genetic, Transfection, Immunoblotting, Blotting, Northern, Transcriptional Activation, Proto-Oncogene Proteins c-jun, Proto-Oncogene Proteins c-fos, Reverse Transcriptase Polymerase Chain Reaction, Drosophila Proteins, RNA, Small Interfering, Immunoprecipitation, Mice

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