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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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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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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DOI: https://doi.org/10.1038/25166
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