Crosstalk between H2A variant-specific modifications impacts vital cell functions

PLoS Genet. 2021 Jun 4;17(6):e1009601. doi: 10.1371/journal.pgen.1009601. eCollection 2021 Jun.


Selection of C-terminal motifs participated in evolution of distinct histone H2A variants. Hybrid types of variants combining motifs from distinct H2A classes are extremely rare. This suggests that the proximity between the motif cases interferes with their function. We studied this question in flowering plants that evolved sporadically a hybrid H2A variant combining the SQ motif of H2A.X that participates in the DNA damage response with the KSPK motif of H2A.W that stabilizes heterochromatin. Our inventory of PTMs of H2A.W variants showed that in vivo the cell cycle-dependent kinase CDKA phosphorylates the KSPK motif of H2A.W but only in absence of an SQ motif. Phosphomimicry of KSPK prevented DNA damage response by the SQ motif of the hybrid H2A.W/X variant. In a synthetic yeast expressing the hybrid H2A.W/X variant, phosphorylation of KSPK prevented binding of the BRCT-domain protein Mdb1 to phosphorylated SQ and impaired response to DNA damage. Our findings illustrate that PTMs mediate interference between the function of H2A variant specific C-terminal motifs. Such interference could explain the mutual exclusion of motifs that led to evolution of H2A variants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Arabidopsis / genetics*
  • Arabidopsis / metabolism
  • Arabidopsis Proteins / genetics*
  • Arabidopsis Proteins / metabolism
  • Cell Culture Techniques
  • Cell Cycle / genetics
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism
  • Cyclin-Dependent Kinases / genetics
  • Cyclin-Dependent Kinases / metabolism
  • DNA Damage
  • Evolution, Molecular
  • Gene Expression Regulation, Plant*
  • Heterochromatin / chemistry
  • Heterochromatin / metabolism
  • Histones / genetics*
  • Histones / metabolism
  • Phosphorylation
  • Plant Cells / metabolism
  • Plants, Genetically Modified
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Processing, Post-Translational*
  • Schizosaccharomyces / genetics*
  • Schizosaccharomyces / metabolism
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Transgenes


  • Arabidopsis Proteins
  • Chromosomal Proteins, Non-Histone
  • Heterochromatin
  • Histones
  • Mdb1 protein, S pombe
  • Protein Isoforms
  • Schizosaccharomyces pombe Proteins
  • CDKA1 protein, Arabidopsis
  • Cyclin-Dependent Kinases