HP1

HP1, short for heterochromatin protein 1, is a family of conserved chromatin-associated proteins that localize to heterochromatin and participate in gene silencing and genome stability. The best known mammalian members are HP1α, HP1β, and HP1γ, encoded by the genes CBX5, CBX1, and CBX3, respectively. The HP1 proteins share a common architecture: an N-terminal chromodomain that binds histone H3 when lysine 9 is trimethylated (H3K9me3), a flexible hinge region, and a C-terminal chromo shadow domain (CSD) that mediates dimerization and interactions with other proteins, often via PxVxL motif-containing partners.

HP1 proteins are enriched at pericentromeric and other constitutive heterochromatin regions, where they help establish and maintain a compact chromatin state. The chromodomain’s recognition of H3K9me3 recruits HP1 to silent regions, and through the CSD, HP1 can recruit additional silencing factors such as the histone methyltransferase SUV39H1, DNA methyltransferases, and corepressor complexes including KAP1/TRIM28. By promoting chromatin compaction and coordinating silencing complexes, HP1 contributes to transcriptional repression, replication timing, and genome stability. In some contexts, HP1γ (often more widely distributed) can also associate with euchromatin and participate in regulated transcription.

Evolutionarily, HP1 homologs are found across eukaryotes, with diversification of isoforms and interactions that reflect lineage-specific regulation of heterochromatin. The protein was first identified in Drosophila melanogaster as a key component of heterochromatin, with conserved functions extended to many other species.