The nonhistone, N-terminal tail of an essential, chimeric H2A variant regulates mitotic H3-S10 dephosphorylation

Genes Dev. 2012 Mar 15;26(6):615-29. doi: 10.1101/gad.182683.111.


H2A.Y is an essential, divergent Tetrahymena thermophila histone variant. It has a long nonhistone N terminus that contains leucine-rich repeats (LRR) and an LRR cap domain with similarity to Sds22p, a regulator of yeast protein phosphatase 1 (PP1) activity in the nucleus. In growing cells, H2A.Y is incorporated into micronuclei only during S phase, which occurs immediately after micronuclear mitosis. Depletion of H2A.Y causes prolonged retention of mitosis-associated histone H3-S10 phosphorylation and mitotic abnormalities that mimic S10E mutation. In cells where H2A.Y is depleted, an inducible chimeric gene, in which the H2A.Y N terminus is attached to H2A.X, is shown to regulate micronuclear H3-S10 phosphorylation. H2A.Y can also be specifically coimmunoprecipitated with a Tetrahymena PP1 ortholog (Ppo1p). Taken together, these results argue that the N terminus of H2A.Y functions to regulate H3-S10 dephosphorylation. This striking in vivo case of "cross-talk" between a H2A variant and a specific post-translational modification of another histone demonstrates a novel function for a histone variant.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • DNA Replication
  • Gene Knockout Techniques
  • Histones / classification
  • Histones / genetics
  • Histones / metabolism*
  • Mitosis*
  • Molecular Sequence Data
  • Mutant Chimeric Proteins / classification
  • Mutant Chimeric Proteins / genetics
  • Mutant Chimeric Proteins / metabolism*
  • Nucleosomes / metabolism
  • Phosphorylation
  • Phylogeny
  • Protein Phosphatase 1 / metabolism
  • Protein Processing, Post-Translational*
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae Proteins / metabolism
  • Tetrahymena thermophila / cytology*
  • Tetrahymena thermophila / metabolism*
  • ras Proteins / metabolism


  • Histones
  • Mutant Chimeric Proteins
  • Nucleosomes
  • Saccharomyces cerevisiae Proteins
  • Protein Phosphatase 1
  • RAS2 protein, S cerevisiae
  • ras Proteins