Crosstalk between H2A variant-specific modifications impacts vital cell functions.

Area of Science:

• Molecular Biology
• Epigenetics
• Plant Biology

Background:

• Histone H2A variants possess distinct C-terminal motifs crucial for their functions.
• Hybrid H2A variants combining motifs from different classes are rare, suggesting functional interference.
• Flowering plants evolved a hybrid H2A variant with DNA damage response (SQ motif) and heterochromatin stabilization (KSPK motif) functions.

Purpose of the Study:

• To investigate the functional interference between C-terminal motifs in hybrid histone H2A variants.
• To understand how post-translational modifications mediate this interference.
• To explain the evolutionary exclusion of certain motifs in H2A variants.

Main Methods:

• Analysis of post-translational modifications (PTMs) in H2A.W variants.
• In vivo studies using flowering plants and synthetic yeast.
• Phosphomimicry experiments to assess motif function.
• Investigating protein binding interactions (Mdb1 to SQ motif).

Main Results:

• CDKA phosphorylates the KSPK motif of H2A.W only when the SQ motif is absent.
• Phosphomimicry of KSPK inhibited the DNA damage response function of the SQ motif in the hybrid variant.
• In yeast, KSPK phosphorylation impaired Mdb1 binding to SQ and DNA damage response.

Conclusions:

• Post-translational modifications mediate functional interference between distinct C-terminal motifs of histone H2A variants.
• This interference mechanism explains the evolutionary divergence and mutual exclusion of these motifs.
• Understanding PTMs is key to deciphering the evolution of histone variant diversity.