HP1α - Heterochromatin organization

The heterochromatin binding protein 1 alpha (HP1α) is a major component of heterochromatin, acting on gene transcription regulation and DNA repair. Structurally, members of the HP1 protein family have a chromodomain and a chromoshadow domain. The former binds to di- and trimethylated lysine 9 (K9) of histone H3 and the latter allows HP1 heterodimerization as well as their interaction with other proteins involved in epigenetic regulation, making HP1 act as an adaptor protein, linking epigenetic regulators to histone marks. HP1 dimerization also binds together two adjacent nucleosomes with methylation markers, providing a molecular mechanism for heterochromatin formation and spreading.

Given the relevance of heterochromatin in gene regulation and its effects on cell function, the non-mutational epigenetic reprogramming is considered one of the hallmarks of cancer. Also patterns of heterochromatin organization are being associated with cell malfunction during the aging process.

To analyze the heterochromatin structure, we fused the HP1α with a fluorescent protein. The variations in number, size and position of HP1α foci inside the nucleus indicates the structural changes in heterochromatin and epigenetic markers of DNA.