The family of Heterochromatin Protein 1 (HP1) ("Chromobox Homolog", CBX) 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, sequesteration of genes to nuclear periphery, transcriptional arrest, maintenance of heterochromatin integrity, gene repression at the single nucleosome level and gene repression by heterochromatization of euchromatin. HP1 proteins are fundamental units of heterochromatin packaging that are enriched at the centromeres and telomeres of nearly all Eukaryoticchromosomes with the notable exception of budding yeast, in which a yeast-specific silencing complex of SIR (silent information regulatory) 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.[1][2]
Paralogs and Orthologs
Three different paralogs of HP1 are found in Drosophila melanogaster, HP1a, HP1b and HP1c. Subsequently orthologs of HP1 were also discovered in S. pombe (Swi6), Xenopus (Xhp1α and Xhp1γ) and Chicken (CHCB1, CHCB2 and CHCB3). In mammals,[3] there are three paralogs: HP1α, HP1β and HP1γ. In Arabidopsis thaliana (a plant), there is one homolog: LIKE HETEROCHROMATIN PROTEIN 1 (LHP1), also known as TERMINAL FLOWER 2 (TFL2).[4]
HP1β interacts with the histone methyltransferase (HMTase) Suv(3-9)h1 and is a component of both pericentric and telomeric heterochromatin.[5][6][7] HP1β is a dosage-dependent modifier of pericentric heterochromatin-induced silencing[8] and silencing is thought to involve a dynamic association of the HP1β chromodomain with the tri-methylated Histone H3 Me(3)K9H3.
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-neighbor cooperative binding. This mode of chromatin interactions could potentially lead to spreading of HP1 along the nucleosome chain. 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.[9]
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Wreggett KA, Hill F, James PS, Hutchings A, Butcher GW, Singh PB (1994). "A mammalian homologue of Drosophila heterochromatin protein 1 (HP1) is a component of constitutive heterochromatin". Cytogenet. Cell Genet. 66 (2): 99–103. doi:10.1159/000133676. PMID8287692.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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Festenstein R, Sharghi-Namini S, Fox M, Roderick K, Tolaini M, Norton T, Saveliev A, Kioussis D, Singh P (December 1999). "Heterochromatin protein 1 modifies mammalian PEV in a dose- and chromosomal-context-dependent manner". Nat. Genet. 23 (4): 457–61. doi:10.1038/70579. PMID10581035.{{cite journal}}: CS1 maint: multiple names: authors list (link)
