Cited by 2,138Genomics and Chromatin DynamicsEpigenetics and DNA MethylationCancer-related gene regulation

Active Genes Are Tri-Methylated at K4 of Histone H3

Santos-Rosa, Helena, Schneider, Robert, Bannister, Andrew J., Sherriff, Julia, Bernstein, Bradley E., Emre, N. C. Tolga, Schreiber, Stuart L., Mellor, Jane +1 more·2002·Nature

Abstract

Lysine methylation of histones in vivo occurs in three states: mono-, di- and tri-methyl. Histone H3 has been found to be di-methylated at lysine 4 (K4) in active euchromatic regions but not in silent heterochromatic sites. Here we show that the Saccharomyces cerevisiae Set1 protein can catalyse di- and tri-methylation of K4 and stimulate the activity of many genes. Using antibodies that discriminate between the di- and tri-methylated state of K4 we show that di-methylation occurs at both inactive and active euchromatic genes, whereas tri-methylation is present exclusively at active genes. It is therefore the presence of a tri-methylated K4 that defines an active state of gene expression. These findings establish the concept of methyl status as a determinant for gene activity and thus extend considerably the complexity of histone modifications.

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Crossref · 10.1038/nature01080

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  • Deposition of H3K4me3 at the 5' regions of actively transcribed genes is facilitated by trithorax group (trxG) protein complexes in coordination with the initiating form of RNA polymerase.

    “The deposition of H3K4me3 at the 5 ′ regions of actively transcribed genes is facilitated by trithorax group (trxG) protein complexes in coordination with the initiating form of RNA polymerase [56,57].”

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Authors
Santos-Rosa, H., Schneider, R., Bannister, A. J., Sherriff, J., Bernstein, B. E., Emre, N. C. T., Schreiber, S. L., Mellor, J., & Kouzarides, T.
Affiliations
  • Cancer Research UK (GB)
  • University of Oxford (GB)
  • Harvard University (US)
  • The Wistar Institute (US)
Corresponding author
Kouzarides, Tony
Venue
Nature
Published
2002-09
Volume
419
Issue
6905
Pages
407-411
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2022936129
Cited by
2,138
References
2
Citations by year
2026: 41 · 2025: 58 · 2024: 71 · 2023: 76 · 2022: 83 · 2021: 95 · 2020: 82 · 2019: 80 · 2018: 62 · 2017: 80 · 2016: 92 · 2015: 83 · 2014: 94 · 2013: 97 · 2012: 100
FWCI
34.88
Type
journal article
Language
en
Open access
closed
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • Site cant be reached (submittedVersion)
Funders
National Institutes of Health
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
H3K4, trimethylation, histone methylation, euchromatin, heterochromatin, gene expression, Saccharomyces cerevisiae, histone modifications, chromatin
MeSH terms
Antibodies, DNA-Binding Proteins, Genes, Fungal, Histones, Inositol, Lysine, Methionine, Methylation, Histone-Lysine N-Methyltransferase, Saccharomyces cerevisiae, Transcription Factors, Transcription, Genetic, Gene Expression Regulation, Fungal, Gene Expression Profiling, Saccharomyces cerevisiae Proteins

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