The HP1 hinge region: more than just a linker for heterochromatin.

Heterochromatin plays an important role in eukaryotic cellular functions, including gene silencing, higher-order chromatin structure, genome stability and so on. Heterochromatin protein 1 (HP1), a key component of heterochromatin, is conserved from fission yeast to mammals. HP1 binds to histone H3K9me, a hallmark of heterochromatin, through its N-terminal chromodomain (CD) and self-dimerizes and recruits other chromatin proteins through its C-terminal chromo shadow domain (CSD), acting as an epigenetic reader. Between the CD and CSD is an unstructured, less conserved hinge region, which has been implicated in nucleic acid binding. The molecular dissection of the fission yeast HP1 orthologue, Chp2, recently reported in this journal, elucidated the cooperative DNA binding of the hinge and N-terminus of the CSD, which contributes to the stable association with heterochromatin and gene silencing. In this commentary, we focus on the mechanisms involving the HP1 hinge region, which is more than a simple linker.