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Active genes are tri-methylated at K4 of histone H3

Author

Listed:
  • Helena Santos-Rosa

    (Wellcome Trust/Cancer Research UK Institute and Department of Pathology)

  • Robert Schneider

    (Wellcome Trust/Cancer Research UK Institute and Department of Pathology)

  • Andrew J. Bannister

    (Wellcome Trust/Cancer Research UK Institute and Department of Pathology)

  • Julia Sherriff

    (University of Oxford)

  • Bradley E. Bernstein

    (Harvard University)

  • N. C. Tolga Emre

    (Wilstar Institute)

  • Stuart L. Schreiber

    (Harvard University)

  • Jane Mellor

    (University of Oxford)

  • Tony Kouzarides

    (Wellcome Trust/Cancer Research UK Institute and Department of Pathology)

Abstract

Lysine methylation of histones in vivo occurs in three states: mono-, di- and tri-methyl1. Histone H3 has been found to be di-methylated at lysine 4 (K4) in active euchromatic regions but not in silent heterochromatic sites2. 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.

Suggested Citation

  • Helena Santos-Rosa & Robert Schneider & Andrew J. Bannister & Julia Sherriff & Bradley E. Bernstein & N. C. Tolga Emre & Stuart L. Schreiber & Jane Mellor & Tony Kouzarides, 2002. "Active genes are tri-methylated at K4 of histone H3," Nature, Nature, vol. 419(6905), pages 407-411, September.
    • Handle: RePEc:nat:nature:v:419:y:2002:i:6905:d:10.1038_nature01080
    DOI: 10.1038/nature01080
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    1. Christine Chevalier & Claudia Chica & Justine Matheau & Adrien Pain & Michael G. Connor & Melanie A. Hamon, 2024. "Epithelial cells maintain memory of prior infection with Streptococcus pneumoniae through di-methylation of histone H3," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Victor Lopez Soriano & Alfredo Dueñas Rey & Rajarshi Mukherjee & Frauke Coppieters & Miriam Bauwens & Andy Willaert & Elfride De Baere, 2024. "Multi-omics analysis in human retina uncovers ultraconserved cis-regulatory elements at rare eye disease loci," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    3. Mengwen Hu & Yu-Han Yeh & Yasuhisa Munakata & Hironori Abe & Akihiko Sakashita & So Maezawa & Miguel Vidal & Haruhiko Koseki & Neil Hunter & Richard M. Schultz & Satoshi H. Namekawa, 2022. "PRC1-mediated epigenetic programming is required to generate the ovarian reserve," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    4. Ting Zhao & Yan Hong & Bowen Yan & Suming Huang & Guo-li Ming & Hongjun Song, 2024. "Epigenetic maintenance of adult neural stem cell quiescence in the mouse hippocampus via Setd1a," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    5. Iksoo Huh & Isabel Mendizabal & Taesung Park & Soojin V Yi, 2018. "Functional conservation of sequence determinants at rapidly evolving regulatory regions across mammals," PLOS Computational Biology, Public Library of Science, vol. 14(10), pages 1-21, October.
    6. Benjamin M. Spector & Mrutyunjaya Parida & Ming Li & Christopher B. Ball & Jeffery L. Meier & Donal S. Luse & David H. Price, 2022. "Differences in RNA polymerase II complexes and their interactions with surrounding chromatin on human and cytomegalovirus genomes," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    7. Mar González-Ramírez & Cecilia Ballaré & Francesca Mugianesi & Malte Beringer & Alexandra Santanach & Enrique Blanco & Luciano Di Croce, 2021. "Differential contribution to gene expression prediction of histone modifications at enhancers or promoters," PLOS Computational Biology, Public Library of Science, vol. 17(9), pages 1-29, September.
    8. Xiaozhen Zhao & Yiming Wang & Bingqin Yuan & Hanxi Zhao & Yujie Wang & Zheng Tan & Zhiyuan Wang & Huijun Wu & Gang Li & Wei Song & Ravi Gupta & Kenichi Tsuda & Zhonghua Ma & Xuewen Gao & Qin Gu, 2024. "Temporally-coordinated bivalent histone modifications of BCG1 enable fungal invasion and immune evasion," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    9. Dongmei Wang & Haimin Li & Navdeep S. Chandel & Yali Dou & Rui Yi, 2023. "MOF-mediated histone H4 Lysine 16 acetylation governs mitochondrial and ciliary functions by controlling gene promoters," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    10. Kana Shimomura & Naoko Hattori & Naoko Iida & Yukari Muranaka & Kotomi Sato & Yuichi Shiraishi & Yasuhito Arai & Natsuko Hama & Tatsuhiro Shibata & Daichi Narushima & Mamoru Kato & Hiroyuki Takamaru &, 2023. "Sleeping Beauty transposon mutagenesis identified genes and pathways involved in inflammation-associated colon tumor development," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    11. Mario Ivanković & Jeremias N. Brand & Luca Pandolfini & Thomas Brown & Martin Pippel & Andrei Rozanski & Til Schubert & Markus A. Grohme & Sylke Winkler & Laura Robledillo & Meng Zhang & Azzurra Codin, 2024. "A comparative analysis of planarian genomes reveals regulatory conservation in the face of rapid structural divergence," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    12. Qi Yu & Xuanyunjing Gong & Yue Tong & Min Wang & Kai Duan & Xinyu Zhang & Feng Ge & Xilan Yu & Shanshan Li, 2022. "Phosphorylation of Jhd2 by the Ras-cAMP-PKA(Tpk2) pathway regulates histone modifications and autophagy," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    13. Shijia Zhu & Guohua Wang & Bo Liu & Yadong Wang, 2013. "Modeling Exon Expression Using Histone Modifications," PLOS ONE, Public Library of Science, vol. 8(6), pages 1-15, June.

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