The nonessential H2A N-terminal tail can function as an essential charge patch on the H2A.Z variant N-terminal tail

Mol Cell Biol. 2003 Apr;23(8):2778-89. doi: 10.1128/MCB.23.8.2778-2789.2003.


Tetrahymena thermophila cells contain three forms of H2A: major H2A.1 and H2A.2, which make up approximately 80% of total H2A, and a conserved variant, H2A.Z. We showed previously that acetylation of H2A.Z was essential (Q. Ren and M. A. Gorovsky, Mol. Cell 7:1329-1335, 2001). Here we used in vitro mutagenesis of lysine residues, coupled with gene replacement, to identify the sites of acetylation of the N-terminal tail of the major H2A and to analyze its function in vivo. Tetrahymena cells survived with all five acetylatable lysines replaced by arginines plus a mutation that abolished acetylation of the N-terminal serine normally found in the wild-type protein. Thus, neither posttranslational nor cotranslational acetylation of major H2A is essential. Surprisingly, the nonacetylatable N-terminal tail of the major H2A was able to replace the essential function of the acetylation of the H2A.Z N-terminal tail. Tail-swapping experiments between H2A.1 and H2A.Z revealed that the nonessential acetylation of the major H2A N-terminal tail can be made to function as an essential charge patch in place of the H2A.Z N-terminal tail and that while the pattern of acetylation of an H2A N-terminal tail is determined by the tail sequence, the effects of acetylation on viability are determined by properties of the H2A core and not those of the N-terminal tail itself.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylation
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Electrochemistry
  • Genes, Protozoan
  • Genetic Variation
  • Histones / chemistry*
  • Histones / genetics
  • Histones / metabolism*
  • Lysine / chemistry
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Mutation
  • Protein Processing, Post-Translational
  • Protozoan Proteins / chemistry*
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Tetrahymena thermophila / genetics
  • Tetrahymena thermophila / metabolism*


  • Histones
  • Protozoan Proteins
  • Recombinant Fusion Proteins
  • Lysine