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Ubiquitylation of the COMPASS component Swd2 links H2B ubiquitylation to H3K4 trimethylation

Nature Cell Biology volume 10, pages 1365–1371 (2008)Cite this article

Abstract

Mono-ubiquitylation of histone H2B correlates with transcriptional activation and is required for di- and trimethylation at Lys 4 on the histone H3 tail (H3K4) by the SET1/COMPASS methyltransferase complex through a poorly characterized trans-tail pathway1,2. Here we show that mono-ubiquitylation of histone H2B promotes ubiquitylation at Lys 68 and Lys 69 of Swd2, the essential component of SET1/COMPASS in Saccharomyces cerevisiae. We found that Rad6/Bre1 ubiquitylation enzymes responsible for H2B ubiquitylation also participate directly in Swd2 modification. Preventing Swd2 or H2B ubiquitylation did not affect Set1 stability, interaction of Swd2 with Set1 or the ability of Swd2 to interact with chromatin. However, we found that mutation of Lys 68 and Lys 69 of Swd2 markedly reduced trimethylation, and to a lesser extent dimethylation, of H3K4 at the 5′-end of transcribing genes without affecting monomethylation. This effect results from the ability of Swd2 ubiquitylation to control recruitment of Spp1, a COMPASS subunit necessary for trimethylation. Our results further indicate that Swd2 is a major H3-binding component of COMPASS. Swd2 thus represents a key factor that mediates crosstalk between H2B ubiquitylation and H3K4 trimethylation on chromatin.

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Figure 1: Ubiquitylation of Swd2 requires Bre1-dependent H2B ubiquitylation and occurs independently of H3K4 methylation.
Figure 2: Ubiquitylation of Lys 68 and Lys 69 of Swd2 controls trimethylation of H3K4.
Figure 3: Ubiquitylation of Lys 68 and Lys 69 of Swd2 does not affect its interaction with Set1 but controls Spp1 recruitment on chromatin.
Figure 4: Swd2 interacts with H3.

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Acknowledgements

We would like to thank P. Nagy for antibodies, G. Divita for help with molecular modelling and V. Oreal for reagents. We are most grateful to S. Dokudovskaya and A. Morillon for very helpful discussions and critical reading of the manuscript. This study was funded by grants from the Agence Nationale pour la Recherche (grant BLAN06-1_134099 to CD) and the Ligue contre le Cancer (C.D. and V.G. laboratories are 'Equipes labellisées'). A.V.P. and M.H. are supported by the Ministère de l'Enseignement Supérieur et de la Recherche and the Association de Recherche contre le Cancer respectively.

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Author notes

  1. Carole Gwizdek and Catherine Dargemont: These authors contributed equally to this work.

Authors and Affiliations

  1. Institut Jacques Monod, Université Paris VII, Université Paris VI, CNRS, 2 Place Jussieu, Tour 43, 75251, Paris Cedex 05, France

    Adeline Vitaliano-Prunier, Alexandra Menant, Maria Hobeika, Carole Gwizdek & Catherine Dargemont

  2. Instabilité du Génome et Cancérogénèse, Institut de Biologie Structurale et Microbiologie, UPR3081, CNRS, 31 chemin Joseph Aiguier, 13402, Marseille cedex 20, France

    Vincent Géli

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Contributions

C.G., V.G. and C.D. designed the experiments; A.V.P., A. M., M.H. and C.G. performed the experiments; A.V.P., A.M., M.H., C.G., V.G.and C.D. analysed the data; V.G. and C.D. wrote the manuscript.

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Correspondence to Carole Gwizdek or Catherine Dargemont.

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Vitaliano-Prunier, A., Menant, A., Hobeika, M. et al. Ubiquitylation of the COMPASS component Swd2 links H2B ubiquitylation to H3K4 trimethylation. Nat Cell Biol 10, 1365–1371 (2008). https://doi.org/10.1038/ncb1796

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