Heterochromatin protein 1

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chromobox homolog 5
Symbol CBX5
Alt. symbols HP1-alpha
Entrez 23468
HUGO 1555
OMIM 604478
RefSeq NM_012117
UniProt P45973
Other data
Locus Chr. 12 q13.13
chromobox homolog 1
Symbol CBX1
Alt. symbols HP1-beta
Entrez 10951
HUGO 1551
OMIM 604511
RefSeq NM_006807
UniProt P83916
Other data
Locus Chr. 17 q21.32
chromobox homolog 3
Symbol CBX3
Alt. symbols HP1-gamma
Entrez 11335
HUGO 1553
OMIM 604477
RefSeq NM_007276
UniProt Q13185
Other data
Locus Chr. 7 p21-15

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 Eukaryotic chromosomes 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[edit]

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 in mammals[edit]

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.

Interacting proteins[edit]

HP1 seems to interact with numerous other proteins/molecules with different cellular functions in different organisms. Some of these HP1 interacting partners are: histone H1, histone H3, methylated K9 histone H3, histone H4, histone methyltransferase, DNA methyltransferase, methyl CpG binding protein MeCP2, and the origin recognition complex protein ORC2

Binding affinity and cooperativity[edit]

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]

See also[edit]


  1. ^ James, T.C.; S.C Elgin (1986). "Identification of a nonhistone chromosomal protein associated with heterochromatin in Drosophila melanogaster and its gene". Mol. Cell. Biol. 6 (11): 3862–3872. PMC 367149Freely accessible. PMID 3099166. 
  2. ^ Eissenberg, J.C., James, T.C., Foster-Hartnett, D.M., Hartnett, T., Ngan, V.K.W., Craig, C., Elgin, S.C.R. (1990). "Mutation in a heterochromatin-specific chromosomal protein is associated with suppression of position-effect variegation in Drosophila melanogaster". Proceedings of the National Academy of Sciences of the United States of America. 87 (24): 9923–7. doi:10.1073/pnas.87.24.9923. PMC 55286Freely accessible. PMID 2124708. 
  3. ^ Singh PB; Miller JR; Pearce J; Kothary R; Burton RD; Paro R; James TC; Gaunt SJ. (February 1991). "A sequence motif found in a Drosophila heterochromatin protein is conserved in animals and plants". Nucleic Acids Res. 19 (4): 789–94. doi:10.1093/nar/19.4.789. PMC 333712Freely accessible. PMID 1708124. 
  4. ^ Kotake, Toshihisa; Takada, Shinobu; Nakahigashi, Kenji; Ohto, Masaaki; Goto, Koji (2003-06-15). "Arabidopsis TERMINAL FLOWER 2 Gene Encodes a Heterochromatin Protein 1 Homolog and Represses both FLOWERING LOCUS T to Regulate Flowering Time and Several Floral Homeotic Genes". Plant and Cell Physiology. 44 (6): 555–564. doi:10.1093/pcp/pcg091. ISSN 0032-0781. PMID 12826620. 
  5. ^ Aagaard L, Laible G, Selenko P, Schmid M, Dorn R, Schotta G, Kuhfittig S, Wolf A, Lebersorger A, Singh PB, Reuter G, Jenuwein T (April 1999). "Functional mammalian homologues of the Drosophila PEV-modifier Su(var)3-9 encode centromere-associated proteins which complex with the heterochromatin component M31". EMBO J. 18 (7): 1923–38. doi:10.1093/emboj/18.7.1923. PMC 1171278Freely accessible. PMID 10202156. 
  6. ^ 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. PMID 8287692. 
  7. ^ Sharma GG; Hwang KK; Pandita RK; Gupta A; Dhar S; Parenteau J; Agarwal M; Worman HJ; Wellinger RJ; Pandita TK. (Nov 2003). "Human Heterochromatin Protein 1 Isoforms HP1Hsα and HP1Hsβ Interfere with hTERT-Telomere Interactions and Correlate with Changes in Cell Growth and Response to Ionizing Radiation". Mol. Cell. Biol. 23 (22): 8363–76. doi:10.1128/MCB.23.22.8363-8376.2003. PMC 262350Freely accessible. PMID 14585993. 
  8. ^ 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. PMID 10581035. 
  9. ^ Teif V.B.; Kepper N.; Yserentant K; Wedemann G.; Rippe K. "Affinity, stoichiometry and cooperativity of heterochromatin protein 1 (HP1) binding to nucleosomal arrays". J. Phys.: Condens. Matter. arXiv:1408.6184Freely accessible. 

Further reading[edit]