The family of heterochromatinprotein 1 consists of highly conserved proteins, which have important functions in the cell nucleus. These functions include gene repression by heterochromatin formation, transcriptional activation, regulation of binding of cohesion complexes to centromeres, sequestration of genes to nuclear periphery, transcriptional arrest, maintenance of heterochromatin integrity, gene repression at the single nucleosome level, gene repression by heterochromatization of euchromatin and DNA repair. HP1 proteins are fundamental units of heterochromatin packaging that are enriched at the centromeres and telomeres of nearly all Eukaryotic chromosomes with the notable exception of budding yeast, in which a yeast-specific silencing complex of SIR proteins serve a similar function. Members of the HP1 family are characterized by an N-terminal chromodomain and a C-terminal chromoshadow domain, separated by a Hinge region. HP1 is also found at euchromatic sites, where its binding correlates with gene repression. HP1 was originally discovered by Tharappel C James and Sarah Elgin in 1986 as a factor in the phenomenon known as position effect variegation in Drosophila melanogaster.
Three different paralogs of HP1 are found in Drosophila melanogaster, HP1a, HP1b and HP1c. Subsequently orthologs of HP1 were also discovered in S. pombe, Xenopus and Chicken and Tetrahymena. In mammals, there are three paralogs: HP1α, HP1β and HP1γ. In Arabidopsis thaliana, there is one homolog: Like Heterochromatin Protein 1, also known as Terminal Flower 2.
HP1β in mammals
HP1β interacts with the histone methyltransferase Suvh1 and is a component of both pericentric and telomeric heterochromatin. HP1β is a dosage-dependent modifier of pericentric heterochromatin-induced silencing and silencing is thought to involve a dynamic association of the HP1β chromodomain with the tri-methylated Histone H3 MeK9H3.
HP1 binding affinity to nucleosomes containing histone H3 methylated at lysine K9 is higher than to those with unmethylated lysine K9. HP1 binds nucleosomes as a dimer and in principle can form multimeric complexes. Some studies have interpreted HP1 binding in terms of nearest-neighborcooperative binding. However, the analysis of available data on HP1 binding to nucleosomal arrays in vitro shows that experimental HP1 binding isotherms can be explained by a simple model without cooperative interactions between neighboring HP1 dimers. Nevertheless, favorable interactions between nearest neighbors of HP1 lead to limited spreading of HP1 and its marks along the nucleosome chain in vivo.
All HP1 isoforms are recruited to DNA at sites of UV-induced damages, at oxidative damages and at DNA breaks. The HP1 protein isoforms are required for DNA repair of these damages. The presence of the HP1 protein isoforms at DNA damages assists with the recruitment of other proteins involved in subsequent DNA repair pathways. The recruitment of the HP1 isoforms to DNA damage is rapid, with half maximum recruitment by 180 seconds in response to UV damage, and a t1/2 of 85 seconds in response to double-strand breaks. This is a bit slower than the recruitment of the very earliest proteins recruited to sites of DNA damage, though HP1 recruitment is still one of the very early steps in DNA repair. Other earlier proteins may be recruited with a t1/2 of 40 seconds for UV damage and a t1/2 of about 1 second in response to double-strand breaks.
