Bipartite chromatin recognition by Hop1 from two diverged Holozoa

Area of Science:

• Molecular Biology
• Genetics
• Structural Biology

Background:

• Meiosis involves ploidy reduction through DNA breakage and recombination.
• Meiotic HORMA domain proteins (HORMADs) orchestrate these events.
• HORMADs feature a central chromatin binding region (CBR) with varying architecture.

Purpose of the Study:

• Determine the high-resolution crystal structures of meiotic HORMAD CBRs from *Schistosoma mansoni* and *Patiria miniata*.
• Investigate the DNA binding mechanism and histone interaction of these CBRs.
• Elucidate how HORMADs bind chromatin and potentially discriminate between chromatin states.

Main Methods:

• High-resolution crystal structure determination.
• In vitro DNA binding assays.
• Nucleosome binding assays.
• Bioinformatic analysis and structure prediction.

Main Results:

• The meiotic HORMAD CBRs from *S. mansoni* and *P. miniata* feature tightly associated plant homeodomain (PHD) and winged helix-turn-helix (wHTH) domains.
• PHD-wHTH CBRs bind duplex DNA via their wHTH domains, with identified key residues crucial for this interaction.
• CBR PHDs likely interact with histone H3 tails, potentially distinguishing between unmethylated and trimethylated H3 lysine 4.
• Holozoa Hop1 CBRs exhibit bipartite binding to nucleosomes in vitro, involving both PHD and wHTH domains.

Conclusions:

• Meiotic HORMADs with PHD-wHTH CBRs can bind chromatin through a dual mechanism.
• These HORMADs may discriminate between different chromatin states, influencing meiotic recombination localization.
• This mechanism provides insight into how HORMADs regulate meiotic processes in diverse eukaryotes.