Abstract
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.
Highlights
Histones represent the major protein component of chromatin
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
We show that cell cycle dependent kinases phosphorylate the KSPK motif identifying the heterochromatin-associated variant H2A.W that evolved in vascular plants
Summary
Histone variants evolved in all core histone families and acquired comparable properties in a convergent manner [1,2,3,4].These variants play major roles in cell fate decisions, development, and disease [5,6,7]. Most multicellular eukaryotes contain three types of H2A variants: H2A, H2A.Z and H2A.X, which are distinguished by specific substitutions in the core domains as well as specific signatures in the C-terminal tails [8,9,10]. The variant H2A.X is defined by the motif SQ[E/D]F present within the C-terminal tail (where F stands for a hydrophobic amino acid). The serine residue of this motif is phosphorylated during the early phase of the DNA damage response [7,11,12,13,14,15,16]. Serine phosphorylation of SQ[E/D]F is essential for DDR [17,18]
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