Properties of Nat4, an N(alpha)-acetyltransferase of Saccharomyces cerevisiae that modifies N termini of histones H2A and H4

Mol Cell Biol. 2009 Jun;29(11):2913-24. doi: 10.1128/MCB.00147-08. Epub 2009 Mar 30.


Nat4, also designated NatD, was previously shown to acetylate the N termini of histones H2A and H4, which have SGGKG and SGRGK N termini (O. K. Song, X. Wang, J. H. Waterborg, and R. Sternglanz, J. Biol. Chem. 278:38109-38112, 2003). The analysis of chimeric proteins with various N-terminal segments of histone H4 fused to iso-1-cytochrome c revealed that efficient acetylation by NatD required at least 30 to 50 amino acid residues of the N terminus of histone H4. This requirement for an extended N terminus is in marked contrast with the major N-terminal acetyl transferases (NATs), i.e., NatA, NatB, and NatC, which require as few as two specific residues and usually no more than four or five. However, similar to the other NATs, NatD is associated with ribosomes. The nat4-Delta strain showed several minor phenotypes, including sensitivity to 3-aminotriazole, benomyl, and thiabendazole. Moreover, these nat4-Delta phenotypes were enhanced in the strain containing K5R K8R K12R replacements in the N-tail of histone H4, suggesting that the lack of N-terminal serine acetylation is synergistic to the lack of acetylation of the H4 N-tail lysines. Thus, N-terminal serine acetylation of histone H4 may be a part of an essential charge patch first described for the histone H2A.Z variant in Tetrahymena species.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylation
  • Acetyltransferases / metabolism*
  • Alleles
  • Amino Acid Sequence
  • Centrifugation, Density Gradient
  • Cytochromes c / chemistry
  • Cytochromes c / metabolism
  • Histone Acetyltransferases
  • Histones / chemistry*
  • Histones / metabolism*
  • Molecular Sequence Data
  • Mutation / genetics
  • N-Terminal Acetyltransferase D
  • Phenotype
  • Polyribosomes / enzymology
  • Protein Processing, Post-Translational*
  • Protein Structure, Secondary
  • Protein Transport
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Substrate Specificity


  • CYC1 protein, S cerevisiae
  • Histones
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • Cytochromes c
  • Acetyltransferases
  • N-Terminal Acetyltransferase D
  • NAT4 protein, S cerevisiae
  • Histone Acetyltransferases