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

Joan Boyes (), Peter Byfield, Yoshihiro Nakatani and Vasily Ogryzko
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Joan Boyes: Section of Gene Function and Regulation, Chester Beatty Laboratories at The Institute of Cancer Research
Peter Byfield: MRC Clinical Sciences Center, Hammersmith Hospital
Yoshihiro Nakatani: Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health
Vasily Ogryzko: Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health

Nature, 1998, vol. 396, issue 6711, 594-598

Abstract: 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.

Date: 1998
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DOI: 10.1038/25166

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