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

• Published in: Nature (London) 1998-12, Vol.396 (6711), p.594-598
• Main Authors: Boyes, Joan, Byfield, Peter, Nakatani, Yoshihiro, Ogryzko, Vasily
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Acetylation; Amino Acid Sequence; Animals; Binding Sites; Biological and medical sciences; Cellular biology; Chickens; Deoxyribonucleic acid; DNA; DNA - metabolism; DNA-Binding Proteins - metabolism; E1A-Associated p300 Protein; Erythroid-Specific DNA-Binding Factors; Fundamental and applied biological sciences. Psychology; GATA1 Transcription Factor; Humanities and Social Sciences; letter; Lysine - metabolism; Mass Spectrometry; Mice; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; multidisciplinary; Nuclear Proteins - metabolism; Protein Binding; Proteins; Science; Science (multidisciplinary); Trans-Activators - metabolism; Transcription Factors - metabolism; Transcription, Genetic; Transcription. Transcription factor. Splicing. Rna processing; Tumor Cells, Cultured; Zinc Fingers
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/25166

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,. 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, TAFII250 (ref. 5) and p300/CBP,). These acetyltransferases also modify certain transcription factors (TFIIEβ, TFIIF, EKLF and p53 (refs 8-10)). GATA-1 is an important transcription factor in the haematopoietic lineage and is essential for terminal differentiation of erythrocytes and megakaryocytes,. It is associated in vivo with the acetyltransferase p300/CBP. 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.