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Regulation of E2F1 activity by acetylation.

During the G(1) phase of the cell cycle, an E2F-RB complex represses transcription, via the recruitment of histone deacetylase activity. Phosphorylation of RB at the G(1)/S boundary generates a pool of 'free' E2F, which then stimulates transcription of S-phase genes. Given that E2F1 activity is stimulated by p300/CBP acetylase and repressed by an RB-associated deacetylase, we asked if E2F1 was subject to modification by acetylation. We show that the p300/CBP-associated factor P/CAF, and to a lesser extent p300/CBP itself, can acetylate E2F1 in vitro and that intracellular E2F1 is acetylated. The acetylation sites lie adjacent to the E2F1 DNA-binding domain and involve lysine residues highly conserved in E2F1, 2 and 3. Acetylation by P/CAF has three functional consequences on E2F1 activity: increased DNA-binding ability, activation potential and protein half-life. These results suggest that acetylation stimulates the functions of the non-RB bound 'free' form of E2F1. Consistent with this, we find that the RB-associated histone deacetylase can deacetylate E2F1. These results identify acetylation as a novel regulatory modification that stimulates E2F1's activation functions.

Pubmed ID: 10675335

Authors

  • Martínez-Balbás MA
  • Bauer UM
  • Nielsen SJ
  • Brehm A
  • Kouzarides T

Journal

The EMBO journal

Publication Data

February 15, 2000

Associated Grants

None

Mesh Terms

  • Acetylation
  • Acetyltransferases
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • Carrier Proteins
  • Cell Cycle Proteins
  • Cell Line
  • DNA
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • G1 Phase
  • Histone Acetyltransferases
  • Histone Deacetylases
  • Humans
  • In Vitro Techniques
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Nuclear Proteins
  • Retinoblastoma Protein
  • Retinoblastoma-Binding Protein 1
  • S Phase
  • Sequence Homology, Amino Acid
  • Trans-Activators
  • Transcription Factor DP1
  • Transcription Factors
  • Transcriptional Activation
  • p300-CBP Transcription Factors