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

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 DNA 1 , 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 ), PCAF 4 , TAF II 250 ( ref. 5 ) and p300/CBP 6 , 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 lineage 11 and is essential for terminal differentiation of erythrocytes and megakaryocytes 12 , 13 . It is associated in vivo with the acetyltransferase p300/CBP 14 . 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.