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Regulation of activity of the transcription factor GATA-1 by acetylation

Nature volume 396, pages 594–598 (1998)Cite this article

Abstract

Modification of histones, DNA-binding proteins found in chromatin, by addition of acetyl groups occurs to a greater degree when the histones are associated with transcriptionally active DNA1,2. A breakthrough in understanding how this acetylation is mediated was the discovery that various transcriptional co-activator proteins have intrinsic histone acetyltransferase activity (for example, Gcn5p (ref. 3), PCAF4, TAFII250 (ref. 5) and p300/CBP6,7). These acetyltransferases also modify certain transcription factors (TFIIEβ, TFIIF, EKLF and p53 (8–10)). GATA-1 is an important transcription factor in the haematopoietic lineage11 and is essential for terminal differentiation of erythrocytes and megakaryocytes12,13. It is associated in vivo with the acetyltransferase p300/CBP14. Here we report that GATA-1 is acetylated in vitro by p300. This significantly increases the amount of GATA-1 bound to DNA and alters the mobility of GATA-1–DNA complexes, suggestive of a conformational change in GATA-1. GATA-1 is also acetylated in vivo and acetylation directly stimulates GATA-1-dependent transcription. Mutagenesis of important acetylated residues shows that there is a relationship between the acetylation and in vivo function of GATA-1. Wepropose that acetylation of transcription factors can alter interactions between these factors and DNA and among different transcription factors, and is an integral part of transcription and differentiation processes.

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Figure 1: The DNA-binding domain of GATA-1 is acetylated by p300.
Figure 2: Binding of acetylated and non-acetylated GATA-1 to DNA.
Figure 3: GATA-1 is acetylated in vivo.
Figure 4: Acetylation of GATA-1 stimulated transcription directly in vivo.

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Acknowledgements

We thank N. Dillon and M. Greaves, in whose laboratories some of this work was done, for support and comments; C. Crane-Robinson for the anti-acetyl-lysine antisera; J. Omichinski for the GATA-1 peptides; M. Zenke for anti-cGATA-1 antisera; M. Pikaart and M. Towatari for plasmids; M.Antoniou for MEL cells; and A. Ashworth, T. Enver, G. Felsenfeld, A. Fisher, J. Mermoud and E. Milot for discussions and comments on the manuscript. J.B. acknowledges support from the Kay Kendall Leukaemia Fund.

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Authors and Affiliations

  1. Section of Gene Function and Regulation, Chester Beatty Laboratories at The Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK

    Joan Boyes

  2. MRC Clinical Sciences Center, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK

    Joan Boyes & Peter Byfield

  3. Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, 20892-2753, Maryland, USA

    Yoshihiro Nakatani & Vasily Ogryzko

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  1. Joan Boyes
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Correspondence to Joan Boyes.

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Boyes, J., Byfield, P., Nakatani, Y. et al. Regulation of activity of the transcription factor GATA-1 by acetylation. Nature 396, 594–598 (1998). https://doi.org/10.1038/25166

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