Archaeal histones coordinate conserved DNA sequence motifs to promote CRISPR adaptive immunity.

A conserved leader motif T2 in Pyrococcus furiosus CRISPR loci is required for both histone-mediated and histone-independent integration, with key base positions at -3 and -4 to -19.

• Why it matters: It was unclear whether archaeal CRISPR leaders carry conserved DNA sequence motifs that are necessary for integration, beyond histone binding.
• What they did: The authors analyzed 542 archaeal CRISPR leaders across Thermococcales and Methanococcales, identifying 36 motifs up to 500 bps upstream, then tested scrambling/truncation and targeted mutations in leader regions 100–400 bps upstream of the P. furiosus CRISPR.
• The result: Disrupting motif T2 ablated integration, with a pyrimidine at position -3 supporting histone-independent integration and basepairs -4 to -19 supporting histone-mediated integration; T2-like sequences are present in most Thermococcales and Methanococcales.

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