Cooperative DNA-binding activities of Chp2 are critical for its function in heterochromatin assembly.

This article investigates the role of DNA-binding activities of Chp2, one of the two heterochromatin protein 1 (HP1) isoforms in the fission yeast *Schizosaccharomyces pombe*, in heterochromatin assembly. The study demonstrates that Chp2 binds DNA through both its hinge region and the N-terminus of its chromoshadow domain (CSD), with basic amino acid residues in these regions cooperatively contributing to DNA binding. Mutations disrupting DNA binding in both domains impair Chp2's stability, reduce its localization to heterochromatic regions, and cause defects in transcriptional silencing, indicating that these DNA-binding activities are critical for Chp2's function in heterochromatin formation. Notably, despite these mutations, Chp2 remains tightly associated with chromatin-enriched fractions independent of known partners Clr4 and Mit1, suggesting additional mechanisms for chromatin association. The findings highlight a unique DNA-binding property of Chp2's CSD not observed in other HP1 proteins and underscore the importance of cooperative DNA interactions for heterochromatin maintenance in fission yeast.