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Histone methylation by the Drosophila epigenetic transcriptional regulator Ash1

Nature volume 419, pages 857–862 (2002)Cite this article

A Retraction to this article was published on 15 April 2015

Abstract

The establishment and maintenance of mitotic and meiotic stable (epigenetic) transcription patterns is fundamental for cell determination and function1. Epigenetic regulation of transcription is mediated by epigenetic activators and repressors, and may require the establishment, ‘spreading’ and maintenance of epigenetic signals2. Although these signals remain unclear, it has been proposed that chromatin structure and consequently post-translational modification of histones may have an important role in epigenetic gene expression3,4. Here we show that the epigenetic activator Ash1 (ref. 5) is a multi-catalytic histone methyl-transferase (HMTase) that methylates lysine residues 4 and 9 in H3 and 20 in H4. Transcriptional activation by Ash1 coincides with methylation of these three lysine residues at the promoter of Ash1 target genes. The methylation pattern placed by Ash1 may serve as a binding surface for a chromatin remodelling complex containing the epigenetic activator Brahma (Brm)6, an ATPase, and inhibits the interaction of epigenetic repressors with chromatin. Chromatin immunoprecipitation indicates that epigenetic activation of Ultrabithorax transcription in Drosophila coincides with trivalent methylation by Ash1 and recruitment of Brm. Thus, histone methylation by Ash1 may provide a specific signal for the establishment of epigenetic, active transcription patterns.

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Figure 1: Ash1 methylates histone H3 and H4.
Figure 2: Ash1 methylates K4 and K9 in H3 and K20 in H4.
Figure 3: Methylation of K4 and K9 in H3 and K20 in H4 coincides with epigenetic activation of transcription by Ash1.
Figure 4: The trivalent methylation pattern generated by Ash1 recruits a Brm-containing chromatin remodelling factor.

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Acknowledgements

We thank M. Meisterernst for anti-dimethylated H4-K20 antibody; A. Shearn and A. Mazo for fly strains; R. Deuring and J. Tamkun for anti-Brm antibody; S. Schönfelder and R. Paro for Trx cDNA; J. Tyler for p55 cDNA; and various members of the laboratory for critical reading of the manuscript. We are grateful to J. Rami for editorial help and Y. Cully for photowork. This work was supported by a Graduiertenkolleg 484 fellowship (Deutshe Forschungsgemeinschaft) (C.B.) and a Tranregio/Sonderforschungsbereich grant (F.S.).

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Authors and Affiliations

  1. Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), Im Neuenheimer Feld 282, 69120, Heidelberg, Germany

    Christian Beisel, Jaime Greene & Frank Sauer

  2. Adolf-Butenandt Institut, Universität München, Schillerstrasse 44, 80336, München, Germany

    Axel Imhof

  3. Department of Biochemistry, 1447 Boyce Hall, University of California, Riverside, California, 92521-0129, USA

    Jaime Greene & Frank Sauer

  4. GSF-Forschungszentrum, Institut für Molekulare Immunologie, Marchionistrasse 25, 81377, München, Germany

    Elisabeth Kremmer

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Correspondence to Frank Sauer.

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Beisel, C., Imhof, A., Greene, J. et al. Histone methylation by the Drosophila epigenetic transcriptional regulator Ash1. Nature 419, 857–862 (2002). https://doi.org/10.1038/nature01126

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