Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지

The Heterochromatin Protein 1 (HP1) Family: Put Away a Bias toward HP1

  • Kwon, So Hee (Stowers Institute for Medical Research) ;
  • Workman, Jerry L. (Stowers Institute for Medical Research)
  • Received : 2008.07.09
  • Accepted : 2008.07.11
  • Published : 2008.09.30
⟨ Previous Next ⟩

Abstract

Heterochromatin protein 1 (HP1) was first described in Drosophila melanogaster as a heterochromatin associated protein with dose-dependent effect on gene silencing. The HP1 family is evolutionarily highly conserved and there are multiple members within the same species. The multi-functionality of HP1 reflects its ability to interact with diverse nuclear proteins, ranging from histones and transcriptional co-repressors to cohesion and DNA replication factors. As its name suggests, HP1 is well-known as a silencing protein found at pericentromeres and telomeres. In contrast to previous views that heterochromatin is transcriptionally inactive; noncoding RNAs transcribed from heterochromatic DNA repeats regulates the assembly and function of heterochromatin ranging from fission yeast to animals. Moreover, more recent progress has shed light on the paradoxical properties of HP1 in the nucleus and has revealed, unexpectedly, its existence in the euchromatin. Therefore, HP1 proteins might participate in both transcription repression in heterochromatin and euchromatin.

Keywords

References

  1. Aagaard, L., Laible, G., Selenko, P., Schmid, M., Dorn, R., Schotta, G., Kuhfittig, S., Wolf, A., Lebersorger, A., Singh, P.B., et al. (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. 18,1923-1938 https://doi.org/10.1093/emboj/18.7.1923
  2. Aagaard, L., Schmid, M., Warburton, P., and Jenuwein, T. (2000). Mitotic phosphorylation of SUV39H1, a novel component of active centromeres, coincides with transient accumulation at mammalian centromeres. J. Cell Sci. 113,817-829
  3. Agarwal, N., Hardt, T., Brero, A, Nowak, D., Rothbauer, U., Becker, A, Leonhardt, H., and Cardoso, M.C. (2007). MeCP2 interacts with HP1 and modulates its heterochromatin association during myogenic differentiation. Nucleic Acids Res. 35, 5402-5408 https://doi.org/10.1093/nar/gkm599
  4. Ainsztein, AM., Kandels-Lewis, S.E., Mackay, AM., and Earnshaw, WC. (1998). INCENP centromere and spindle targeting: identification of essential conserved motifs and involvement of heterochromatin protein HP1. J. Cell BioI. 143,1763-1774 https://doi.org/10.1083/jcb.143.7.1763
  5. Ait-Si-Ali, S., Guasconi, V., Fritsch, L., Yahi, H., Sekhri, R., Naguibneva, I., Robin, P., Cabon, F., Polesskaya, A, and Harel-Bellan, A (2004). A Suv39h-dependent mechanism for silencing Sphase genes in differentiating but not in cycling cells. EMBO J. 23, 605-615 https://doi.org/10.1038/sj.emboj.7600074
  6. Andrulis, E.D., Neiman, AM., Zappulla, D.C., and Sternglanz, R. (1998). Perinuclear localization of chromatin facilitates transcriptional silencing. Nature 394, 592-595 https://doi.org/10.1038/29100
  7. Auth, T., Kunkel, E., and Grummt, F. (2006). Interaction between HP1alpha and replication proteins in mammalian cells. Exp. Cell Res. 312, 3349-3359 https://doi.org/10.1016/j.yexcr.2006.07.014
  8. Ayoub, N., Noma, K., Isaac, S., Kahan, T., Grewal, S.I., and Cohen, A. (2003). A novel jmjC domain protein modulates heterochromatization in fission yeast. Mol. Cell. Biol. 23, 4356-4370 https://doi.org/10.1128/MCB.23.12.4356-4370.2003
  9. Ayyanathan, K., Lechner, M.S., Bell, P., Maul, G.G., Schultz, D.C., Yamada, Y., Tanaka, K., Torigoe, K., and Rauscher, F.J. 3rd. (2003). Regulated recruitment of HP1 to a euchromatic gene induces mitotically heritable, epigenetic gene silencing: a mammalian cell culture model of gene variegation. Genes Dev. 17, 1855-1869 https://doi.org/10.1101/gad.1102803
  10. Bachman, K.E., Rountree, M.R., and Baylin, S.B. (2001). Dnmt3a and Dnmt3b are transcriptional repressors that exhibit unique localization properties to heterochromatin. J. Biol. Chem. 276, 32282-32287 https://doi.org/10.1074/jbc.M104661200
  11. Badugu, R., Yoo, Y., Singh, P.B., and Kellum, R. (2005). Mutations in the heterochromatin protein 1 (HP1) hinge domain affect HP1 protein interactions and chromosomal distribution. Chromosoma 113, 370-384 https://doi.org/10.1007/s00412-004-0324-2
  12. Bailis, J.M., Bernard, P., Antonelli, R., Allshire, R.C., and Forsburg, S.L. (2003). Hsk1-Dfp1 is required for heterochromatinmediated cohesion at centromeres. Nat. Cell Biol. 5, 1111-1116 https://doi.org/10.1038/ncb1069
  13. Bannister, A.J., Zegerman, P., Partridge, J.F., Miska, E.A., Thomas, J.O., Allshire, R.C., and Kouzarides, T. (2001). Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature 410, 120-124 https://doi.org/10.1038/35065138
  14. Baulcombe, D. (2004). RNA silencing in plants. Nature 431 356-363 https://doi.org/10.1038/nature02874
  15. Brasher, S.V., Smith, B.O., Fogh, R.H., Nietlispach, D., Thiru, A., Nielsen, P.R., Broadhurst, R.W., Ball, L.J., Murzina, N.V., and Laue, E.D. (2000). The structure of mouse HP1 suggests a unique mode of single peptide recognition by the shadow chromo domain dimer. EMBO J. 19, 1587-1597 https://doi.org/10.1093/emboj/19.7.1587
  16. Brower-Toland, B., Findley, S.D., Jiang, L., Liu, L., Yin, H., Dus, M., Zhou, P., Elgin, S.C., and Lin, H. (2007). Drosophila PIWI associates with chromatin and interacts directly with HP1a. Genes Dev. 21, 2300-2311 https://doi.org/10.1101/gad.1564307
  17. Cam, H.P., Sugiyama, T., Chen, E.S., Chen, X., FitzGerald, P.C., and Grewal, S.I. (2005). Comprehensive analysis of heterochromatin- and RNAi-mediated epigenetic control of the fission yeast genome. Nat. Genet. 37, 809-819 https://doi.org/10.1038/ng1602
  18. Carrozza, M.J., Li, B., Florens, L., Suganuma, T., Swanson, S.K., Lee, K.K., Shia, W.J., Anderson, S., Yates, J., Washburn, M.P., et al. (2005). Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription. Cell 123, 581-592 https://doi.org/10.1016/j.cell.2005.10.023
  19. Chin, H.G., Esteve, P.O., Pradhan, M., Benner, J., Patnaik, D., Carey, M.F., and Pradhan, S. (2007). Automethylation of G9a and its implication in wider substrate specificity and HP1 binding. Nucleic Acids Res. 35, 7313-7323 https://doi.org/10.1093/nar/gkm726
  20. Cleard, F., Delattre, M., and Spierer, P. (1997). SU(VAR)3-7, a Drosophila heterochromatin-associated protein and companion of HP1 in the genomic silencing of position-effect variegation. EMBO J. 16, 5280-5288 https://doi.org/10.1093/emboj/16.17.5280
  21. Clegg, N.J., Honda, B.M., Whitehead, I.P., Grigliatti, T.A., Wakimoto, B., Brock, H.W., Lloyd, V.K., and Sinclair, D.A. (1998). Suppressors of position-effect variegation in Drosophila melanogaster affect expression of the heterochromatic gene light in the absence of a chromosome rearrangement. Genome / National Research Council Canada = Genome / Conseil National de Recherches Canada 41, 495-503
  22. Cortes, A., Huertas, D., Fanti, L., Pimpinelli, S., Marsellach, F.X., Pina, B., and Azorin, F. (1999). DDP1, a single-stranded nucleic acid-binding protein of Drosophila, associates with pericentric heterochromatin and is functionally homologous to the yeast Scp160p, which is involved in the control of cell ploidy. EMBO J.18, 3820-3833 https://doi.org/10.1093/emboj/18.13.3820
  23. Couteau, F., Guerry, F., Muller, F., and Palladino, F. (2002). A heterochromatin protein 1 homologue in Caenorhabditis elegans acts in germline and vulval development. EMBO Rep. 3, 235-241 https://doi.org/10.1093/embo-reports/kvf051
  24. Cowell, I.G., Aucott, R., Mahadevaiah, S.K., Burgoyne, P.S., Huskisson, N., Bongiorni, S., Prantera, G., Fanti, L., Pimpinelli, S., Wu, R.I=et al. (2002). Heterochromatin, HP1 and methylation at lysine 9 of histone H3 in animals. Chromosoma 111, 22-36 https://doi.org/10.1007/s00412-002-0182-8
  25. Cowieson, N.P., Partridge, J.F., Allshire, R.C., and McLaughlin, P.J. (2000). Dimerisation of a chromo shadow domain and distinctions from the chromodomain as revealed by structural analysis. Curr. Biol. 10, 517-525 https://doi.org/10.1016/S0960-9822(00)00467-X
  26. Cryderman, D.E., Grade, S.K., Li, Y., Fanti, L., Pimpinelli, S., and Wallrath, L.L. (2005). Role of Drosophila HP1 in euchromatic gene expression. Dev. Dyn. 232, 767-774 https://doi.org/10.1002/dvdy.20310
  27. Czvitkovich, S., Sauer, S., Peters, A.H., Deiner, E., Wolf, A., Laible, G., Opravil, S., Beug, H., and Jenuwein, T. (2001). Overexpression of the SUV39H1 histone methyltransferase induces altered proliferation and differentiation in transgenic mice. Mech. Dev. 107, 141-153 https://doi.org/10.1016/S0925-4773(01)00464-6
  28. De Lucia, F., Ni, J.Q., Vaillant, C., and Sun, F.L. (2005). HP1 modulates the transcription of cell-cycle regulators in Drosophila melanogaster. Nucleic Acids Res. 33, 2852-2858 https://doi.org/10.1093/nar/gki584
  29. Delattre, M., Spierer, A., Tonka, C.H., and Spierer, P. (2000). The genomic silencing of position-effect variegation in Drosophila melanogaster: interaction between the heterochromatinassociated proteins Su(var)3-7 and HP1. J. Cell Sci.113, 4253-4261
  30. Demakova, O.V., Pokholkova, G.V., Kolesnikova, T.D., Demakov, S.A., Andreyeva, E.N., Belyaeva, E.S., and Zhimulev, I.F. (2007). The SU(VAR)3-9/HP1 complex differentially regulates the compaction state and degree of underreplication of X chromosome pericentric heterochromatin in Drosophila melanogaster. Genetics 175, 609-620 https://doi.org/10.1534/genetics.106.062133
  31. Eissenberg, J.C., James, T.C., Foster-Hartnett, D.M., Hartnett, T., Ngan, V., and Elgin, S.C. (1990). Mutation in a heterochromatinspecific chromosomal protein is associated with suppression of position-effect variegation in Drosophila melanogaster. Proc. Natl. Acad. Sci. USA 87, 9923-9927
  32. Eissenberg, J.C., Morris, G.D., Reuter, G., and Hartnett, T. (1992). The heterochromatin-associated protein HP-1 is an essential protein in Drosophila with dosage-dependent effects on positioneffect variegation. Genetics 131, 345-352
  33. Elgin, S.C., and Grewal, S.I. (2003). Heterochromatin: silence is golden. Curr. Biol. 13, R895-898 https://doi.org/10.1016/j.cub.2003.11.006
  34. Fanti, L., Berloco, M., Piacentini, L., and Pimpinelli, S. (2003). Chromosomal distribution of heterochromatin protein 1 (HP1) in Drosophila: a cytological map of euchromatic HP1 binding sites. Genetica 117,135-147 https://doi.org/10.1023/A:1022971407290
  35. Fanti, L., Giovinazzo, G., Berloco, M., and Pimpinelli, S. (1998). The heterochromatin protein 1 prevents telomere fusions in Drosophila. Mol. Cell 2, 527-538
  36. Fox, C.A., Ehrenhofer-Murray, A.E., Loo, S., and Rine, J. (1997). The origin recognition complex, SIR1, and the S phase requirement for silencing. Science 276, 1547-1551 https://doi.org/10.1126/science.276.5318.1547
  37. Frankel, S., Sigel, E.A., Craig, C., Elgin, S.C., Mooseker, M.S., and Artavanis-Tsakonas, S. (1997). An actin-related protein in Drosophila colocalizes with heterochromatin protein 1 in pericentric heterochromatin. J. Cell Sci. 110, 1999-2012
  38. Fukagawa, T., Nogami, M., Yoshikawa, M., Ikeno, M., Okazaki, T., Takami, Y., Nakayama, T., and Oshimura, M. (2004). Dicer is essential for formation of the heterochromatin structure in vertebrate cells. Nat. Cell Biol. 6, 784-791 https://doi.org/10.1038/ncb1155
  39. Furuta, K., Chan, E.K., Kiyosawa, K., Reimer, G., Luderschmidt, C., and Tan, E.M. (1997). Heterochromatin protein HP1Hsbeta (p25beta) and its localization with centromeres in mitosis. Chromosoma 106, 11-19 https://doi.org/10.1007/s004120050219
  40. Gaillard, P.H., Martini, E.M., Kaufman, P.D., Stillman, B., Moustacchi, E., and Almouzni, G. (1996). Chromatin assembly coupled to DNA repair: a new role for chromatin assembly factor I. Cell 86, 887-896 https://doi.org/10.1016/S0092-8674(00)80164-6
  41. Garcia-Cao, M., O'Sullivan, R., Peters, A.H., Jenuwein, T., and Blasco, M.A. (2004). Epigenetic regulation of telomere length in mammalian cells by the Suv39h1 and Suv39h2 histone methyltransferases. Nat. Genet. 36, 94-99 https://doi.org/10.1038/ng1278
  42. Greil, F., de Wit, E., Bussemaker, H.J., and van Steensel, B. (2007). HP1 controls genomic targeting of four novel heterochromatin proteins in Drosophila. EMBO J. 26, 741-751 https://doi.org/10.1038/sj.emboj.7601527
  43. Grewal, S.I., and Moazed, D. (2003). Heterochromatin and epigenetic control of gene expression. Science 301, 798-802 https://doi.org/10.1126/science.1086887
  44. Grishok, A., Sinskey, J.L., and Sharp, P.A. (2005). Transcriptional silencing of a transgene by RNAi in the soma of C. elegans. Genes Dev. 19, 683-696 https://doi.org/10.1101/gad.1247705
  45. Hall, I.M., Shankaranarayana, G.D., Noma, K., Ayoub, N., Cohen, A., and Grewal, S.I. (2002). Establishment and maintenance of a heterochromatin domain. Science 297, 2232-2237 https://doi.org/10.1126/science.1076466
  46. Hayakawa, T., Haraguchi, T., Masumoto, H., and Hiraoka, Y. (2003). Cell cycle behavior of human HP1 subtypes: distinct molecular domains of HP1 are required for their centromeric localization during interphase and metaphase. J. Cell Sci. 116, 3327-3338 https://doi.org/10.1242/jcs.00635
  47. Houlard, M., Berlivet, S., Probst, A.V., Quivy, J.P., Hery, P., Almouzni, G., and Gerard, M. (2006). CAF-1 is essential for heterochromatin organization in pluripotent embryonic cells. PLoS Genet. 2, e181 https://doi.org/10.1371/journal.pgen.0020181
  48. Jacobs, S.A., and Khorasanizadeh, S. (2002). Structure of HP1 chromodomain bound to a lysine 9-methylated histone H3 tail. Science 295, 2080-2083 https://doi.org/10.1126/science.1069473
  49. Jacobs, S.A., Taverna, S.D., Zhang, Y., Briggs, S.D., Li, J., Eissenberg, J.C., Allis, C.D., and Khorasanizadeh, S. (2001). Specificity of the HP1 chromo domain for the methylated N-terminus of histone H3. EMBO J. 20, 5232-5241 https://doi.org/10.1093/emboj/20.18.5232
  50. James, T.C., and Elgin, S.C. (1986). Identification of a nonhistone chromosomal protein associated with heterochromatin in Drosophila melanogaster and its gene. Mol. Cell. Biol. 6, 3862-3872 https://doi.org/10.1128/MCB.6.11.3862
  51. James, T.C., Eissenberg, J.C., Craig, C., Dietrich, V., Hobson, A., and Elgin, S.C. (1989). Distribution patterns of HP1, a heterochromatin- associated nonhistone chromosomal protein of Drosophila. Eur. J. Cell Biol. 50, 170-180
  52. Johansson, A.M., Stenberg, P., Pettersson, F., and Larsson, J. (2007). POF and HP1 bind expressed exons, suggesting a balancing mechanism for gene regulation. PLoS Genet. 3, e209 https://doi.org/10.1371/journal.pgen.0030209
  53. Kanellopoulou, C., Muljo, S.A., Kung, A.L., Ganesan, S., Drapkin, R., Jenuwein, T., Livingston, D.M., and Rajewsky, K. (2005). Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes Dev. 19, 489-50 https://doi.org/10.1101/gad.1248505
  54. Kato, M., Sasaki, M., Mizuno, S., and Harata, M. (2001). Novel actin-related proteins in vertebrates: similarities of structure and expression pattern to Arp6 localized on Drosophila heterochromatin. Gene 268, 133-140 https://doi.org/10.1016/S0378-1119(01)00420-6
  55. Kaufman, P.D., Kobayashi, R., Kessler, N., and Stillman, B. (1995). The p150 and p60 subunits of chromatin assembly factor I: a molecular link between newly synthesized histones and DNA replication. Cell 81, 1105-1114 https://doi.org/10.1016/S0092-8674(05)80015-7
  56. Koering, C.E., Pollice, A., Zibella, M.P., Bauwens, S., Puisieux, A., Brunori, M., Brun, C., Martins, L., Sabatier, L., Pulitzer, J.F.,=et al. (2002). Human telomeric position effect is determined by chromosomal context and telomeric chromatin integrity. EMBO Rep. 3, 1055-1061 https://doi.org/10.1093/embo-reports/kvf215
  57. Koike, N., Maita, H., Taira, T., Ariga, H., and Iguchi-Ariga, S.M. (2000). Identification of heterochromatin protein 1 (HP1) as a phosphorylation target by Pim-1 kinase and the effect of phosphorylation on the transcriptional repression function of HP1(1). FEBS Lett. 467, 17-21 https://doi.org/10.1016/S0014-5793(00)01105-4
  58. Kourmouli, N., Theodoropoulos, P.A., Dialynas, G., Bakou, A., Politou, A.S., Cowell, I.G., Singh, P.B., and Georgatos, S.D. (2000). Dynamic associations of heterochromatin protein 1 with the nuclear envelope. EMBO J. 19, 6558-6568 https://doi.org/10.1093/emboj/19.23.6558
  59. Kouzarides, T. (2007). Chromatin modifications and their function. Cell 128, 693-705 https://doi.org/10.1016/j.cell.2007.02.005
  60. Lachner, M., O'Carroll, D., Rea, S., Mechtler, K., and Jenuwein, T. (2001). Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410, 116-120 https://doi.org/10.1038/35065132
  61. Le Douarin, B., Nielsen, A.L., Garnier, J.M., Ichinose, H., Jeanmougin, F., Losson, R., and Chambon, P. (1996). A possible involvement of TIF1 alpha and TIF1 beta in the epigenetic control of transcription by nuclear receptors. EMBO J. 15, 6701-6715
  62. Lechner, M.S., Begg, G.E., Speicher, D.W., and Rauscher, F.J., 3rd (2000). Molecular determinants for targeting heterochromatin protein 1-mediated gene silencing: direct chromoshadow domain- KAP-1 corepressor interaction is essential. Mol. Cell. Biol. 20, 6449-6465 https://doi.org/10.1128/MCB.20.17.6449-6465.2000
  63. Lehming, N., Le Saux, A., Schuller, J., and Ptashne, M. (1998). Chromatin components as part of a putative transcriptional repressing complex. Proc. Natl. Acad. Sci. USA 95, 7322-7326
  64. Li, Y., Kirschmann, D.A., and Wallrath, L.L. (2002). Does heterochromatin protein 1 always follow code? Proc. Natl. Acad. Sci. USA 99, 16462-16469
  65. Li, B., Gogol, M., Carey, M., Lee, D., Seidel, C., and Workman, J.L. (2007). Combined action of PHD and chromo domains directs the Rpd3S HDAC to transcribed chromatin. Science 316, 1050-1054 https://doi.org/10.1126/science.1139004
  66. Linder, B., Gerlach, N., and Jackle, H. (2001). The Drosophila homolog of the human AF10 is an HP1-interacting suppressor of position effect variegation. EMBO Rep. 2, 211-216 https://doi.org/10.1093/embo-reports/kve039
  67. Lomberk, G., Bensi, D., Fernandez-Zapico, M.E., and Urrutia, R. (2006). Evidence for the existence of an HP1-mediated subcode within the histone code. Nat. Cell Biol. 8, 407-415 https://doi.org/10.1038/ncb1383
  68. Lu, B.Y., Emtage, P.C., Duyf, B.J., Hilliker, A.J., and Eissenberg, J.C. (2000). Heterochromatin protein 1 is required for the normal expression of two heterochromatin genes in Drosophila. Genetics 155, 699-708
  69. Maison, C., and Almouzni, G. (2004). HP1 and the dynamics of heterochromatin maintenance. Nat. Rev. Mol. Cell. Biol. 5, 296-304 https://doi.org/10.1038/nrm1355
  70. Maison, C., Bailly, D., Peters, A.H., Quivy, J.P., Roche, D., Taddei, A., Lachner, M., Jenuwein, T., and Almouzni, G. (2002). Higherorder structure in pericentric heterochromatin involves a distinct pattern of histone modification and an RNA component. Nat. Genet. 30, 329-334 https://doi.org/10.1038/ng843
  71. Matzke, M.A., and Birchler, J.A. (2005). RNAi-mediated pathways in the nucleus. Nat. Rev. Genet 6, 24-35 https://doi.org/10.1038/nrg1500
  72. Maul, G.G., Jensen, D.E., Ishov, A.M., Herlyn, M., and Rauscher, F.J., 3rd (1998). Nuclear redistribution of BRCA1 during viral infection. Cell Growth Differ. 9, 743-755
  73. McDowell, T.L., Gibbons, R.J., Sutherland, H., O'Rourke, D.M., Bickmore, W.A., Pombo, A., Turley, H., Gatter, K., Picketts, D.J., Buckle, V.J., et al. (1999). Localization of a putative transcriptional regulator (ATRX) at pericentromeric heterochromatin and the short arms of acrocentric chromosomes. Proc. Natl. Acad. Sci. USA 96, 13983-13988
  74. Millar, C.B., and Grunstein, M. (2006). Genome-wide patterns of histone modifications in yeast. Nat. Rev. Mol. Cell. Biol. 7, 657-666 https://doi.org/10.1038/nrm1986
  75. Minc, E., Allory, Y., Worman, H.J., Courvalin, J.C., and Buendia, B. (1999). Localization and phosphorylation of HP1 proteins during the cell cycle in mammalian cells. Chromosoma 108, 220-234 https://doi.org/10.1007/s004120050372
  76. Minc, E., Courvalin, J.C., and Buendia, B. (2000). HP1gamma associates with euchromatin and heterochromatin in mammalian nuclei and chromosomes. Cytogenet. Cell Genet. 90, 279-284 https://doi.org/10.1159/000056789
  77. Moggs, J.G., Grandi, P., Quivy, J.P., Jonsson, Z.O., Hubscher, U., Becker, P.B., and Almouzni, G. (2000). A CAF-1-PCNAmediated chromatin assembly pathway triggered by sensing DNA damage. Mol. Cell. Biol. 20, 1206-1218 https://doi.org/10.1128/MCB.20.4.1206-1218.2000
  78. Motamedi, M.R., Verdel, A., Colmenares, S.U., Gerber, S.A., Gygi, S.P., and Moazed, D. (2004). Two RNAi complexes, RITS and RDRC, physically interact and localize to noncoding centromeric RNAs. Cell 119, 789-802 https://doi.org/10.1016/j.cell.2004.11.034
  79. Muchardt, C., Guilleme, M., Seeler, J.S., Trouche, D., Dejean, A., and Yaniv, M. (2002). Coordinated methyl and RNA binding is required for heterochromatin localization of mammalian HP1alpha. EMBO Rep. 3, 975-981 https://doi.org/10.1093/embo-reports/kvf194
  80. Murchison, E.P., Partridge, J.F., Tam, O.H., Cheloufi, S., and Hannon, G.J. (2005). Characterization of Dicer-deficient murine embryonic stem cells. Proc. Natl. Acad. Sci. USA 102, 12135- 12140
  81. Murzina, N., Verreault, A., Laue, E., and Stillman, B. (1999). Heterochromatin dynamics in mouse cells: interaction between chromatin assembly factor 1 and HP1 proteins. Mol. Cell 4, 529-540 https://doi.org/10.1016/S1097-2765(00)80204-X
  82. Nakahigashi, K., Jasencakova, Z., Schubert, I., and Goto, K. (2005). The Arabidopsis heterochromatin protein1 homolog (TERMINAL FLOWER2) silences genes within the euchromatic region but not genes positioned in heterochromatin. Plant Cell Physiol. 46, 1747-1756 https://doi.org/10.1093/pcp/pci195
  83. Nakayama, J., Rice, J.C., Strahl, B.D., Allis, C.D., and Grewal, S.I. (2001). Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly. Science 292, 110-113 https://doi.org/10.1126/science.1060118
  84. Netzer, C., Rieger, L., Brero, A., Zhang, C.D., Hinzke, M., Kohlhase, J., and Bohlander, S.K. (2001). SALL1, the gene mutated in Townes-Brocks syndrome, encodes a transcriptional repressor which interacts with TRF1/PIN2 and localizes to pericentromeric heterochromatin. Hum. Mol. Genet. 10, 3017-3024 https://doi.org/10.1093/hmg/10.26.3017
  85. Nielsen, A.L., Ortiz, J.A., You, J., Oulad-Abdelghani, M., Khechumian, R., Gansmuller, A., Chambon, P., and Losson, R. (1999). Interaction with members of the heterochromatin protein 1 (HP1) family and histone deacetylation are differentially involved in transcriptional silencing by members of the TIF1 family. EMBO J. 18, 6385-6395 https://doi.org/10.1093/emboj/18.22.6385
  86. Nielsen, A.L., Oulad-Abdelghani, M., Ortiz, J.A., Remboutsika, E., Chambon, P., and Losson, R. (2001a). Heterochromatin formation in mammalian cells: interaction between histones and HP1 proteins. Mol. Cell 7, 729-739 https://doi.org/10.1016/S1097-2765(01)00218-0
  87. Nielsen, S.J., Schneider, R., Bauer, U.M., Bannister, A.J., Morrison, A., O'Carroll, D., Firestein, R., Cleary, M., Jenuwein, T., Herrera, R.E., et al. (2001b). Rb targets histone H3 methylation and HP1 to promoters. Nature 412, 561-565 https://doi.org/10.1038/35087620
  88. Nielsen, A.L., Sanchez, C., Ichinose, H., Cervino, M., Lerouge, T., Chambon, P., and Losson, R. (2002). Selective interaction between the chromatin-remodeling factor BRG1 and the heterochromatin- associated protein HP1alpha. EMBO J. 21, 5797-5806 https://doi.org/10.1093/emboj/cdf560
  89. Noma, K., Sugiyama, T., Cam, H., Verdel, A., Zofall, M., Jia, S., Moazed, D., and Grewal, S.I. (2004). RITS acts in cis to promote RNA interference-mediated transcriptional and post-transcriptional silencing. Nat. Genet. 36, 1174-1180 https://doi.org/10.1038/ng1452
  90. Nonaka, N., Kitajima, T., Yokobayashi, S., Xiao, G., Yamamoto, M., Grewal, S.I., and Watanabe, Y. (2002). Recruitment of cohesin to heterochromatic regions by Swi6/HP1 in fission yeast. Nat. Cell Biol. 4, 89-93 https://doi.org/10.1038/ncb739
  91. Obuse, C., Iwasaki, O., Kiyomitsu, T., Goshima, G., Toyoda, Y., and Yanagida, M. (2004). A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1. Nat. Cell Biol. 6, 1135-1141 https://doi.org/10.1038/ncb1187
  92. Ogawa, H., Ishiguro, K., Gaubatz, S., Livingston, D.M., and Nakatani, Y. (2002). A complex with chromatin modifiers that occupies E2F- and Myc-responsive genes in G0 cells. Science 296, 1132-1136 https://doi.org/10.1126/science.1069861
  93. Okada, Y., Suzuki, T., Sunden, Y., Orba, Y., Kose, S., Imamoto, N., Takahashi, H., Tanaka, S., Hall, W.W., Nagashima, K., et al. (2005). Dissociation of heterochromatin protein 1 from lamin B receptor induced by human polyomavirus agnoprotein: role in nuclear egress of viral particles. EMBO Rep. 6, 452-457 https://doi.org/10.1038/sj.embor.7400406
  94. Pak, D.T., Pflumm, M., Chesnokov, I., Huang, D.W., Kellum, R., Marr, J., Romanowski, P., and Botchan, M.R. (1997). Association of the origin recognition complex with heterochromatin and HP1 in higher eukaryotes. Cell 91, 311-323 https://doi.org/10.1016/S0092-8674(00)80415-8
  95. Pal-Bhadra, M., Leibovitch, B.A., Gandhi, S.G., Rao, M., Bhadra, U., Birchler, J.A., and Elgin, S.C. (2004). Heterochromatic silencing and HP1 localization in Drosophila are dependent on the RNAi machinery. Science 303, 669-672 https://doi.org/10.1126/science.1092653
  96. Partridge, J.F., Scott, K.S., Bannister, A.J., Kouzarides, T., and Allshire, R.C. (2002). cis-acting DNA from fission yeast centromeres mediates histone H3 methylation and recruitment of silencing factors and cohesin to an ectopic site. Curr. Biol. 12, 1652-1660 https://doi.org/10.1016/S0960-9822(02)01177-6
  97. Perrini, B., Piacentini, L., Fanti, L., Altieri, F., Chichiarelli, S., Berloco, M., Turano, C., Ferraro, A., and Pimpinelli, S. (2004). HP1 controls telomere capping, telomere elongation, and telomere silencing by two different mechanisms in Drosophila. Mol. Cell 15, 467-476 https://doi.org/10.1016/j.molcel.2004.06.036
  98. Piacentini, L., Fanti, L., Berloco, M., Perrini, B., and Pimpinelli, S. (2003). Heterochromatin protein 1 (HP1) is associated with induced gene expression in Drosophila euchromatin. J. Cell Biol. 161, 707-714 https://doi.org/10.1083/jcb.200303012
  99. Pindyurin, A.V., Boldyreva, L.V., Shloma, V.V., Kolesnikova, T.D., Pokholkova, G.V., Andreyeva, E.N., Kozhevnikova, E.N., Ivanoschuk, I.G., Zarutskaya, E.A., Demakov, S.A., et al. (2008). Interaction between the Drosophila heterochromatin proteins SUUR and HP1. J. Cell Sci. 121, 1693-1703 https://doi.org/10.1242/jcs.018655
  100. Platero, J.S., Hartnett, T., and Eissenberg, J.C. (1995). Functional analysis of the chromo domain of HP1. EMBO J. 14, 3977-3986
  101. Polioudaki, H., Kourmouli, N., Drosou, V., Bakou, A., Theodoropoulos, P.A., Singh, P.B., Giannakouros, T., and Georgatos, S.D. (2001). Histones H3/H4 form a tight complex with the inner nuclear membrane protein LBR and heterochromatin protein 1. EMBO Rep. 2, 920-925 https://doi.org/10.1093/embo-reports/kve199
  102. Pyrpasopoulou, A., Meier, J., Maison, C., Simos, G., and Georgatos, S.D. (1996). The lamin B receptor (LBR) provides essential chromatin docking sites at the nuclear envelope. EMBO J. 15, 7108-7119
  103. Richards, E.J., and Elgin, S.C. (2002). Epigenetic codes for heterochromatin formation and silencing: rounding up the usual suspects. Cell 108, 489-500 https://doi.org/10.1016/S0092-8674(02)00644-X
  104. Rohr, O., Lecestre, D., Chasserot-Golaz, S., Marban, C., Avram, D., Aunis, D., Leid, M., and Schaeffer, E. (2003). Recruitment of Tat to heterochromatin protein HP1 via interaction with CTIP2 inhibits human immunodeficiency virus type 1 replication in microglial cells. J. Virol. 77, 5415-5427 https://doi.org/10.1128/JVI.77.9.5415-5427.2003
  105. Ryan, R.F., Schultz, D.C., Ayyanathan, K., Singh, P.B., Friedman, J.R., Fredericks, W.J., and Rauscher, F.J., 3rd (1999). KAP-1 corepressor protein interacts and colocalizes with heterochromatic and euchromatic HP1 proteins: a potential role for Kruppel-associated box-zinc finger proteins in heterochromatinmediated gene silencing. Mol. Cell. Biol. 19, 4366-4378 https://doi.org/10.1128/MCB.19.6.4366
  106. Savitsky, M., Kravchuk, O., Melnikova, L., and Georgiev, P. (2002). Heterochromatin protein 1 is involved in control of telomere elongation in Drosophila melanogaster. Mol. Cell. Biol. 22, 3204-3218 https://doi.org/10.1128/MCB.22.9.3204-3218.2002
  107. Scholzen, T., Endl, E., Wohlenberg, C., van der Sar, S., Cowell, I.G., Gerdes, J., and Singh, P.B. (2002). The Ki-67 protein interacts with members of the heterochromatin protein 1 (HP1) family: a potential role in the regulation of higher-order chromatin structure. J. Pathol. 196, 135-144 https://doi.org/10.1002/path.1016
  108. Schotta, G., Ebert, A., Krauss, V., Fischer, A., Hoffmann, J., Rea, S., Jenuwein, T., Dorn, R., and Reuter, G. (2002). Central role of Drosophila SU(VAR)3-9 in histone H3-K9 methylation and heterochromatic gene silencing. EMBO J. 21, 1121-1131 https://doi.org/10.1093/emboj/21.5.1121
  109. Schultz, D.C., Friedman, J.R., and Rauscher, F.J., 3rd (2001). Targeting histone deacetylase complexes via KRAB-zinc finger proteins: the PHD and bromodomains of KAP-1 form a cooperative unit that recruits a novel isoform of the Mi-2alpha subunit of NuRD. Genes Dev. 15, 428-443 https://doi.org/10.1101/gad.869501
  110. Schultz, D.C., Ayyanathan, K., Negorev, D., Maul, G.G., and Rauscher, F.J., 3rd (2002). SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zincfinger proteins. Genes Dev. 16, 919-932 https://doi.org/10.1101/gad.973302
  111. Schwendemann, A., Matkovic, T., Linke, C., Klebes, A., Hofmann, A., and Korge, G. (2008). Hip, an HP1-interacting protein, is a haplo- and triplo-suppressor of position effect variegation. Proc. Natl. Acad. Sci. USA 105, 204-209
  112. Seeler, J.S., Marchio, A., Sitterlin, D., Transy, C., and Dejean, A. (1998). Interaction of SP100 with HP1 proteins: a link between the promyelocytic leukemia-associated nuclear bodies and the chromatin compartment. Proc. Natl. Acad. Sci. USA 95, 7316- 7321
  113. Shareef, M.M., King, C., Damaj, M., Badagu, R., Huang, D.W., and Kellum, R. (2001). Drosophila heterochromatin protein 1 (HP1)/origin recognition complex (ORC) protein is associated with HP1 and ORC and functions in heterochromatin-induced silencing. Mol. Biol. Cell 12, 1671-1685 https://doi.org/10.1091/mbc.12.6.1671
  114. Shi, S., Calhoun, H.C., Xia, F., Li, J., Le, L., and Li, W.X. (2006). JAK signaling globally counteracts heterochromatic gene silencing. Nat. Genet. 38, 1071-1076 https://doi.org/10.1038/ng1860
  115. Shibahara, K., and Stillman, B. (1999). Replication-dependent marking of DNA by PCNA facilitates CAF-1-coupled inheritance of chromatin. Cell 96, 575-585 https://doi.org/10.1016/S0092-8674(00)80661-3
  116. Shilatifard, A. (2006). Chromatin modifications by methylation and ubiquitination: implications in the regulation of gene expression. Ann. Rev. Biochem. 75, 243-269 https://doi.org/10.1146/annurev.biochem.75.103004.142422
  117. Sijen, T., and Plasterk, R.H. (2003). Transposon silencing in the Caenorhabditis elegans germ line by natural RNAi. Nature 426, 310-314 https://doi.org/10.1038/nature02107
  118. Singh, P.B., Miller, J.R., Pearce, J., Kothary, R., Burton, R.D., Paro, R., James, T.C., and Gaunt, S.J. (1991). A sequence motif found in a Drosophila heterochromatin protein is conserved in animals and plants. Nucleic Acids Res. 19, 789-794 https://doi.org/10.1093/nar/19.4.789
  119. Smothers, J.F., and Henikoff, S. (2001). The hinge and chromo shadow domain impart distinct targeting of HP1-like proteins. Mol. Cell. Biol. 21, 2555-2569 https://doi.org/10.1128/MCB.21.7.2555-2569.2001
  120. Song, K., Jung, Y., Jung, D., and Lee, I. (2001). Human Ku70 interacts with heterochromatin protein 1alpha. J. Biol. Chem. 276, 8321-8327 https://doi.org/10.1074/jbc.M008779200
  121. Turner, B.M., Birley, A.J., and Lavender, J. (1992). Histone H4 isoforms acetylated at specific lysine residues define individual chromosomes and chromatin domains in Drosophila polytene nuclei. Cell 69, 375-384 https://doi.org/10.1016/0092-8674(92)90417-B
  122. Tzeng, T.Y., Lee, C.H., Chan, L.W., and Shen, C.K. (2007). Epigenetic regulation of the Drosophila chromosome 4 by the histone H3K9 methyltransferase dSETDB1. Proc. Natl. Acad. Sci. USA 104, 12691-12696
  123. Vakoc, C.R., Mandat, S.A., Olenchock, B.A., and Blobel, G.A. (2005). Histone H3 lysine 9 methylation and HP1gamma are associated with transcription elongation through mammalian chromatin. Mol. Cell 19, 381-391 https://doi.org/10.1016/j.molcel.2005.06.011
  124. Vassallo, M.F., and Tanese, N. (2002). Isoform-specific interaction of HP1 with human TAFII130. Proc. Natl. Acad. Sci. USA 99, 5919-5924
  125. Verdel, A., Jia, S., Gerber, S., Sugiyama, T., Gygi, S., Grewal, S.I., and Moazed, D. (2004). RNAi-mediated targeting of heterochromatin by the RITS complex. Science 303, 672-676 https://doi.org/10.1126/science.1093686
  126. Vermaak, D., Henikoff, S., and Malik, H.S. (2005). Positive selection drives the evolution of rhino, a member of the heterochromatin protein 1 family in Drosophila. PLoS Genet. 1, 96-108
  127. Volpe, T.A., Kidner, C., Hall, I.M., Teng, G., Grewal, S.I., and Martienssen, R.A. (2002). Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science 297, 1833-1837 https://doi.org/10.1126/science.1074973
  128. Wakimoto, B.T., and Hearn, M.G. (1990). The effects of chromosome rearrangements on the expression of heterochromatic genes in chromosome 2L of Drosophila melanogaster. Genetics 125, 141-154
  129. Williams, L., and Grafi, G. (2000). The retinoblastoma protein - a bridge to heterochromatin. Trends Plant Sci. 5, 239-240 https://doi.org/10.1016/S1360-1385(00)01653-8
  130. Ye, Q., and Worman, H.J. (1996). Interaction between an integral protein of the nuclear envelope inner membrane and human chromodomain proteins homologous to Drosophila HP1. J. Biol. Chem. 271,14653-14656 https://doi.org/10.1074/jbc.271.25.14653
  131. Ye, Q., Callebaut, I., Pezhman, A., Courvalin, J.C., and Worman, H.J. (1997). Domain-specific interactions of human HP1-type chromodomain proteins and inner nuclear membrane protein LBR. J. Biol. Chem. 272, 14983-14989 https://doi.org/10.1074/jbc.272.23.14983
  132. Yin, H., and Lin, H. (2007). An epigenetic activation role of Piwi and a Piwi-associated piRNA in Drosophila melanogaster. Nature 450, 304-308 https://doi.org/10.1038/nature06263
  133. Zhang, C.L., McKinsey, T.A., and Olson, E.N. (2002). Association of class II histone deacetylases with heterochromatin protein 1: potential role for histone methylation in control of muscle differentiation. Mol. Cell. Biol. 22, 7302-7312 https://doi.org/10.1128/MCB.22.20.7302-7312.2002
  134. Zhao, T., and Eissenberg, J.C. (1999). Phosphorylation of heterochromatin protein 1 by casein kinase II is required for efficient heterochromatin binding in Drosophila. J. Biol. Chem. 274, 15095-15100 https://doi.org/10.1074/jbc.274.21.15095
  135. Zhao, T., Heyduk, T., and Eissenberg, J.C. (2001). Phosphorylation site mutations in heterochromatin protein 1 (HP1) reduce or eliminate silencing activity. J. Biol. Chem. 276, 9512-9518 https://doi.org/10.1074/jbc.M010098200
  136. Zofall, M., and Grewal, S.I. (2006). Swi6/HP1 recruits a JmjC domain protein to facilitate transcription of heterochromatic repeats. Mol. Cell 22, 681-692 https://doi.org/10.1016/j.molcel.2006.05.010