Regulation of Activity of the Transcription Factor GATA-1 by Acetylation

Nature. 1998 Dec 10;396(6711):594-8. doi: 10.1038/25166.

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 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, PCAF, TAF(II)250 and p300/CBP. These acetyltransferases also modify certain transcription factors (TFIIEbeta, TFIIF, EKLF and p53). 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. We propose 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Acetylation
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Chickens
  • DNA / metabolism
  • DNA-Binding Proteins / metabolism*
  • E1A-Associated p300 Protein
  • Erythroid-Specific DNA-Binding Factors
  • GATA1 Transcription Factor
  • Lysine / metabolism
  • Mass Spectrometry
  • Mice
  • Molecular Sequence Data
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Trans-Activators / metabolism*
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Tumor Cells, Cultured
  • Zinc Fingers*

Substances

  • DNA-Binding Proteins
  • Erythroid-Specific DNA-Binding Factors
  • GATA1 Transcription Factor
  • Gata1 protein, mouse
  • Nuclear Proteins
  • Trans-Activators
  • Transcription Factors
  • DNA
  • E1A-Associated p300 Protein
  • Ep300 protein, mouse
  • Lysine