Skip to main content
Log in

Replication of heterochromatin: insights into mechanisms of epigenetic inheritance

  • Review
  • Published:
Chromosoma Aims and scope Submit manuscript

Abstract

Heterochromatin is composed of tightly condensed chromatin in which the histones are deacetylated and methylated, and specific nonhistone proteins are bound. Additionally, in vertebrates and plants, the DNA within heterochromatin is methylated. As the heterochromatic state is stably inherited, replication of heterochromatin requires not only duplication of the DNA but also a reinstallment of the appropriate protein and DNA modifications. Thus replication of heterochromatin provides a framework for understanding mechanisms of epigenetic inheritance. In recent studies, roles have been identified for replication factors in reinstating heterochromatin, particularly functions for origin recognition complex, proliferating cell nuclear antigen, and chromatin-assembly factor 1 in recruiting the heterochromatin binding protein HP1, a histone methyltransferase, a DNA methyltransferase, and a chromatin remodeling complex. Potential mechanistic links between these factors are discussed. In some cells, replication of the heterochromatin is blocked, and in Drosophila this inhibition is mediated by a chromatin binding protein SuUR.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Ahmad K, Henikoff S (2002) Epigenetic consequences of nucleosome dynamics. Cell 111:281–284

    PubMed  CAS  Google Scholar 

  • Ahmed S, Saini S, Arora S, Singh J (2001) Chromodomain protein Swi6-mediated role of DNA polymerase alpha in establishment of silencing in fission yeast. J Biol Chem 276:47814–47821

    PubMed  CAS  Google Scholar 

  • Araujo FD, Knox JD, Szyf M, Price GB, Zannis-Hadjopoulos M (1998) Concurrent replication and methylation at mammalian origins of replication. Mol Cell Biol 18:3475–3482

    PubMed  CAS  Google Scholar 

  • Avni D, Yang H, Martelli F, Hofmann F, ElShamy WM, Ganesan G, Scully R, Livingston DM (2003) Active localization of the retinoblastoma protein in chromatin and its response to S phase DNA damage. Mol Cell 12:735–746

    PubMed  CAS  Google Scholar 

  • Badugu R, Shareef MM, Kellum R (2003) Novel Drosophila heterochromatin protein 1 (HP1)/origin recognition complex-associated protein (HOAP) repeat motif in HP1/HOAP interactions and chromocenter associations. J Biol Chem 278:34491–34498

    PubMed  CAS  Google Scholar 

  • Bannister AJ, Zegerman P, Partridge JF, Miska EA, Thomas JO, Allshire RC, Kouzarides T (2001) Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature 410:120–124

    PubMed  CAS  Google Scholar 

  • Bell SP, Dutta A (2002) DNA replication in eukaryotic cells. Annu Rev Biochem 71:333–374

    PubMed  CAS  Google Scholar 

  • Bell SP, Mitchell J, Leber J, Kobayashi R, Stillman B (1995) The multidomain structure of Orc1p reveals similarity to regulators of DNA replication and transcriptional silencing. Cell 83:563–568

    PubMed  CAS  Google Scholar 

  • Belyaeva ES, Zhimulev IF, Volkova EI, Alekseyenko AA, Moshkin YM, Koryakov DE (1998) Su(UR)ES: a gene suppressing DNA underreplication in intercalary and pericentric heterochromatin of Drosophila melanogaster polytene chromosomes. Proc Natl Acad Sci U S A 95:7532–7537

    PubMed  CAS  Google Scholar 

  • Belyaeva ES, Boldyreva LV, Volkova EI, Nanayev RA, Alekseyenko AA, Zhimulev IF (2003) Effect of the Suppressor of Underreplication (SuUR) gene on position-effect variegation silencing in Drosophila melanogaster. Genetics 165:1209–1220

    PubMed  CAS  Google Scholar 

  • Belyakin SN, Christophides GK, Alekseyenko AA, Kriventseva EV, Belyaeva ES, Nanyev RA, Makunin IV, Kafatos FC, Zhimulev IF, Heidelberg Fly Array Consortium (2005) Genomic analysis of Drosophila chromosome underreplication reveals a link between replication control and transcriptional territories. Proc Natl Acad Sci U S A 102:8269–8274

    PubMed  CAS  Google Scholar 

  • Bosco G, Du W, Orr-Weaver TL (2001) DNA replication control through interaction of E2F-RB and the origin recognition complex. Nat Cell Biol 3:289–295

    PubMed  CAS  Google Scholar 

  • Bozhenok L, Wade PA, Varga-Weisz P (2002) WSTF–ISWI chromatin remodeling complex targets heterochromatic replication foci. EMBO J 21:2231–2241

    PubMed  CAS  Google Scholar 

  • Cheutin T, McNairn AJ, Jenuwein T, Gilbert DM, Singh PB, Misteli T (2003) Maintenance of stable heterochromatin domains by dynamic HP1 binding. Science 299:721–725

    PubMed  CAS  Google Scholar 

  • Chuang LS, Ian HI, Koh TW, Ng HH, Xu G, Li BF (1997) Human DNA-(cytosine-5) methyltransferase–PCNA complex as a target for p21WAF1. Science 277:1996–2000

    PubMed  CAS  Google Scholar 

  • Collins N, Poot RA, Kukimoto I, Garcia-Jimenez C, Dellaire G, Varga-Weisz PD (2002) An ACF1–ISWI chromatin-remodeling complex is required for DNA replication through heterochromatin. Nat Genet 32:627–632

    PubMed  CAS  Google Scholar 

  • Corona DF, Tamkun JW (2004) Multiple roles for ISWI in transcription, chromosome organization and DNA replication. Biochim Biophys Acta 1677:113–119

    PubMed  CAS  Google Scholar 

  • Craig JM (2005) Heterochromatin—many flavours, common themes. BioEssays 27:17–28

    PubMed  CAS  Google Scholar 

  • Czermin B, Imhof A (2003) The sounds of silence—histone deacetylation meets histone methylation. Genetica 117:159–164

    PubMed  CAS  Google Scholar 

  • de la Serna IL, Imbalzano AN (2002) Unfolding heterochromatin for replication. Nat Genet 32:560–562

    PubMed  Google Scholar 

  • Dillin A, Rine J (1997) Separable functions of ORC5 in replication initiation and silencing in Saccharomyces cerevisiae. Genetics 147:1053–1062

    PubMed  CAS  Google Scholar 

  • Dillon N, Festenstein R (2002) Unravelling heterochromatin: competition between positive and negative factors regulates accessibility. Trends Genet 18:252–258

    PubMed  CAS  Google Scholar 

  • Edgar BA, Orr-Weaver TL (2001) Endoreplication cell cycles: more for less. Cell 105:297–306

    PubMed  CAS  Google Scholar 

  • Ekwall K, Olsson T, Turner BM, Cranston G, Allshire RC (1997) Transient inhibition of histone deacetylation alters the structural and functional imprint at fission yeast centromeres. Cell 91:1021–1032

    PubMed  CAS  Google Scholar 

  • Enomoto S, Berman J (1998) Chromatin assembly factor I contributes to the maintenance, but not the re-establishment, of silencing at the yeast silent mating loci. Genes Dev 12:219–232

    PubMed  CAS  Google Scholar 

  • Fischle W, Wang Y, Allis CD (2003) Histone and chromatin cross-talk. Curr Opin Cell Biol 15:172–183

    PubMed  CAS  Google Scholar 

  • Fukagawa T, Nogami M, Yoshikawa M, Ikeno M, Okazaki T, Takami Y, Nakayama T, Oshimura M (2004) Dicer is essential for formation of the heterochromatin structure in vertebrate cells. Nat Cell Biol 6:784–791

    PubMed  CAS  Google Scholar 

  • Fuks F, Hurd PJ, Deplus R, Kouzarides T (2003a) The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase. Nucleic Acids Res 31:2305–2312

    PubMed  CAS  Google Scholar 

  • Fuks F, Hurd PJ, Wolf D, Nan X, Bird AP, Kouzarides T (2003b) The methyl-CpG-binding protein MeCP2 links DNA methylation to histone methylation. J Biol Chem 278:4035–4040

    PubMed  CAS  Google Scholar 

  • Fuss J, Linn S (2002) Human DNA polymerase epsilon colocalizes with proliferating cell nuclear antigen and DNA replication late, but not early, in S phase. J Biol Chem 277:8658–8666

    PubMed  CAS  Google Scholar 

  • Fyodorov DV, Blower MD, Karpen GH, Kadonaga JT (2004) Acf1 confers unique activities to ACF/CHRAC and promotes the formation rather than disruption of chromatin in vivo. Genes Dev 18:170–183

    PubMed  CAS  Google Scholar 

  • Gilbert DM (2002) Replication timing and transcriptional control: beyond cause and effect. Curr Opin Cell Biol 14:377–383

    PubMed  CAS  Google Scholar 

  • Gonzalo S, Garcia-Cao M, Fraga MF, Schotta G, Peters AH, Cotter SE, Eguia R, Dean DC, Esteller M, Jenuwein T, Blasco MA (2005) Role of the RB1 family in stabilizing histone methylation at constitutive heterochromatin. Nat Cell Biol 7:420–428

    PubMed  CAS  Google Scholar 

  • Greil F, van der Kraan I, Delrow J, Smothers JE, de Wit E, Bussemaker HJ, van Driel R, Henikoff S, van Steensel B (2003) Distinct HP1 and Su(var)3-9 complexes bind to sets of developmentally coexpressed genes depending on chromosomal location. Genes Dev 17:2825–2838

    PubMed  CAS  Google Scholar 

  • Gruss C, Wu J, Koller T, Sogo JM (1993) Disruption of the nucleosomes at the replication fork. EMBO J 12:4533–4545

    PubMed  CAS  Google Scholar 

  • Henderson DS, Banga SS, Grigliatti TA, Boyd JB (1994) Mutagen sensitivity and suppression of position-effect variegation result from mutations in mus209, the Drosophila gene encoding PCNA. EMBO J 13:1450–1459

    PubMed  CAS  Google Scholar 

  • Henikoff S (2000) Heterochromatin function in complex genomes. Biochim Biophys Acta 1470:1–8

    Google Scholar 

  • Henikoff S, Furuyama T, Ahmad K (2004) Histone variants, nucleosomal assembly and epigenetic inheritance. Trends Genet 20:320–326

    PubMed  CAS  Google Scholar 

  • Huang Y (2002) Transcriptional silencing in Saccharomyces cerevisiae and Schizosaccharomyces pombe. Nucleic Acids Res 30:1465–1482

    PubMed  CAS  Google Scholar 

  • Huang DW, Fanti L, Pak DT, Botchan MR, Pimpinelli S, Kellum R (1998) Distinct cytoplasmic and nuclear fractions of Drosophila heterochromatin protein 1: their phosphorylation levels and associations with origin recognition complex proteins. J Cell Biol 142:307–318

    PubMed  CAS  Google Scholar 

  • Hubscher U, Maga G, Spadari S (2002) Eukaryotic DNA polymerases. Annu Rev Biochem 71:133–163

    PubMed  CAS  Google Scholar 

  • Huertas D, Cortes A, Casanova J, Azorin F (2004) Drosophila DDP1, a multi-KH-domain protein, contributes to centromeric silencing and chromosome segregation. Curr Biol 14:1611–1620

    PubMed  CAS  Google Scholar 

  • Iida T, Suetake I, Tajima S, Morioka H, Ohta S, Obuse C, Tsurimoto T (2002) PCNA clamp facilitates action of DNA cytosine methyltransferase 1 on hemimethylated DNA. Genes Cells 7:997–1007

    PubMed  CAS  Google Scholar 

  • Iizuka M, Stillman B (1999) Histone acetyltransferase HBO1 interacts with the ORC1 subunit of the human initiator protein. J Biol Chem 274:23027–23034

    PubMed  CAS  Google Scholar 

  • Jiang YH, Bressler J, Beaudet AL (2004) Epigenetics and human disease. Annu Rev Genomics Hum Genet 5:479–510

    PubMed  CAS  Google Scholar 

  • Kamakaka RT, Biggins S (2005) Histone variants: deviants? Genes Dev 19:295–310

    PubMed  CAS  Google Scholar 

  • Kanellopoulou C, Muljo SA, Kung AL, Ganesan S, Drapkin R, Jenuwein T, Livingston DM, Rajewsky K (2005) Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes Dev 19:489–501

    PubMed  CAS  Google Scholar 

  • Katan-Khaykovich Y, Struhl K (2005) Heterochromatin formation involves changes in histone modifications over multiple cell generations. EMBO J 24:2138–2149

    PubMed  CAS  Google Scholar 

  • Kirchmaier AL, Rine J (2001) DNA replication-independent silencing in S. cerevisiae. Science 291:646–650

    PubMed  CAS  Google Scholar 

  • Krude T (1995) Chromatin assembly factor 1 (CAF-1) colocalizes with replication foci in HeLa cell nuclei. Exp Cell Res 220:304–311

    PubMed  CAS  Google Scholar 

  • Krude T (1999) Chromatin assembly during DNA replication in somatic cells. Eur J Biochem 263

  • Lachner M, O'Carroll D, Rea S, Mechtler K, Jenuwein T (2001) Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410:116–120

    PubMed  CAS  Google Scholar 

  • Leach TJ, Chotkowski HL, Wotring MG, Dilwith RL, Glaser RL (2000) Replication of heterochromatin and structure of polytene chromosomes. Mol Cell Biol 20:6308–6316

    PubMed  CAS  Google Scholar 

  • Leatherwood J, Vas A (2003) Connecting ORC and heterochromatin: why? Cell Cycle 2:573–575

    PubMed  CAS  Google Scholar 

  • Lehnertz B, Ueda Y, Derijck AA, Braunschweig U, Perez-Burgos L, Kubicek S, Chen T, Li E, Jenuwein T, Peters AH (2003) Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin. Curr Biol 13:1192–1200

    PubMed  CAS  Google Scholar 

  • Leonhardt H, Page AW, Weier HU, Bestor TH (1992) A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei. Cell 71:865–873

    PubMed  CAS  Google Scholar 

  • Li YC, Cheng TH, Gartenberg MR (2001) Establishment of transcriptional silencing in the absence of DNA replication. Science 291:650–653

    PubMed  CAS  Google Scholar 

  • Lidonnici MR, Rossi R, Paixao S, Mendoza-Maldonado R, Paolinelli R, Arcangeli C, Giacca M, Biamonti G, Montecucco A (2004) Subnuclear distribution of the largest subunit of the human origin recognition complex during the cell cycle. J Cell Sci 117:5221–5231

    PubMed  CAS  Google Scholar 

  • Lilly MA, Spradling AC (1996) The Drosophila endocycle is controlled by Cyclin E and lacks a checkpoint ensuring S-phase completion. Genes Dev 10:2514–2526

    PubMed  CAS  Google Scholar 

  • Lippman Z, Martienssen R (2004) The role of RNA interference in heterochromatic silencing. Nature 431:364–370

    PubMed  CAS  Google Scholar 

  • Loupart M-L, Krause SA, Heck MMS (2000) Aberrant replication timing induces defective chromosome condensation in Drosophila ORC2 mutants. Curr Biol 10:1547–1556

    PubMed  CAS  Google Scholar 

  • Maga G, Hubscher U (2003) Proliferating cell nuclear antigen (PCNA): a dancer with many partners. J Cell Sci 116:3051–3060

    PubMed  CAS  Google Scholar 

  • Maison C, Almouzni G (2004) HP1 and the dynamics of heterochromatin maintenance. Nat Rev Mol Cell Biol 5:296–304

    PubMed  CAS  Google Scholar 

  • Majka J, Burgers PM (2004) The PCNA-RFC families of DNA clamps and clamp loaders. Prog Nucleic Acid Res Mol Biol 78:227–260

    Article  PubMed  CAS  Google Scholar 

  • Makunin IV, Volkova EI, Belyaeva ES, Nabirochkina EN, Pirrotta V, Zhimulev IF (2002) The Drosophila suppressor of underreplication protein binds to late-replicating regions of polytene chromosomes. Genetics 160:1023–1034

    PubMed  CAS  Google Scholar 

  • Martens JHA, O'Sullivan RJ, Braunschweig U, Opravil S, Radolf M, Steinlein P, Jenuwein T (2005) The profile of repeat-associated histone lysine methylation states in the mouse epigenome. EMBO J 24:800–812

    PubMed  CAS  Google Scholar 

  • Matzke MA, Birchler JA (2005) RNAi-mediated pathways in the nucleus. Nat Rev Genet 6:24–35

    PubMed  CAS  Google Scholar 

  • McNairn AJ, Gilbert DM (2003) Epigenomic replication: linking epigenetics to DNA replication. BioEssays 25:647–656

    PubMed  CAS  Google Scholar 

  • Mello JA, Almouzni G (2001) The ins and outs of nucleosome assembly. Curr Opin Genet Dev 11:136–141

    PubMed  CAS  Google Scholar 

  • Moshkin YM, Alekseyenko AA, Semeshin VF, Spierer A, Spierer P, Makarevich GF, Belyaeva ES, Zhimulev IF (2001) The bithorax complex of Drosophila melanogaster: underreplication and morphology in polytene chromosomes. Proc Natl Acad Sci U S A 98:570–574

    PubMed  CAS  Google Scholar 

  • Motamedi MR, Verdel A, Colmenares SU, Gerber SA, Gygi SP, Moazed D (2004) Two RNAi complexes, RITS and RDRC, physically interact and localize to noncoding centromeric RNAs. Cell 119:789–802

    PubMed  CAS  Google Scholar 

  • Murzina N, Verreault A, Laue E, Stillman B (1999) Heterochromatin dynamics in mouse cells: interaction between chromatin assembly factor 1 and HP1 proteins. Mol Cell 4:529–540

    PubMed  CAS  Google Scholar 

  • Nakayama J, Rice JC, Strahl BD, Allis CD, Grewal SI (2001) Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly. Science 292:110–113

    PubMed  CAS  Google Scholar 

  • Nielsen AL, Oulad-Abdelghani M, Ortiz JA, Remboutsika E, Chambon P, Losson R (2001) Heterochromatin formation in mammalian cells: interaction between histones and HP1 proteins. Mol Cell 7:729–739

    PubMed  CAS  Google Scholar 

  • Pak DT, Pflumm M, Chesnokov I, Huang DW, Kellum R, Marr J, Romanowski P, Botchan MR (1997) Association of the origin recognition complex with heterochromatin and HP1 in higher eukaryotes. Cell 91:311–323

    PubMed  CAS  Google Scholar 

  • Pal-Bhadra M, Leibovitch BA, Gandhi SG, Rao M, Bhadra U, Birchler JA, Elgin SC (2004) Heterochromatic silencing and HP1 localization in Drosophila are dependent on the RNAi machinery. Science 303:669–672

    PubMed  CAS  Google Scholar 

  • Poot RA, Bozhenok L, van den Berg DL, Steffensen S, Ferreira F, Grimaldi M, Gilbert N, Ferreira J, Varga-Weisz PD (2004) The Williams syndrome transcription factor interacts with PCNA to target chromatin remodelling by ISWI to replication foci. Nat Cell Biol 6:1236–1244

    PubMed  CAS  Google Scholar 

  • Prasanth SG, Prasanth KV, Siddiqui K, Spector DL, Stillman B (2004) Human Orc2 localizes to centrosomes, centromeres and heterochromatin during chromosome inheritance. EMBO J 23:2651–2663

    PubMed  CAS  Google Scholar 

  • Quivy JP, Roche D, Kirschner D, Tagami H, Nakatani Y, Almouzni G (2004) A CAF-1 dependent pool of HP1 during heterochromatin duplication. EMBO J 23:3516–3526

    PubMed  CAS  Google Scholar 

  • Reese BE, Bachman KE, Baylin SB, Rountree MR (2003) The methyl-CpG binding protein MBD1 interacts with the p150 subunit of chromatin assembly factor 1. Mol Cell Biol 23:3226–3236

    PubMed  CAS  Google Scholar 

  • Ridgway P, Almouzni G (2000) CAF-1 and the inheritance of chromatin states: at the crossroads of DNA replication and repair. J Cell Sci 113:2647–2658

    PubMed  CAS  Google Scholar 

  • Royzman I, Hayashi-Hagihara A, Dej KJ, Bosco G, Lee JY, Orr-Weaver TL (2002) The E2F cell cycle regulator is required for Drosophila nurse cell DNA replication and apoptosis. Mech Dev 119:225–237

    PubMed  CAS  Google Scholar 

  • Rudkin GT (1969) Non replicating DNA in Drosophila. Genetics 61(Suppl):227–238

    PubMed  CAS  Google Scholar 

  • Sarraf SA, Stancheva I (2004) Methyl-CpG binding protein MBD1 couples histone H3 methylation at lysine 9 by SETDB1 to DNA replication and chromatin assembly. Mol Cell 15:595–605

    PubMed  CAS  Google Scholar 

  • Schotta G, Ebert A, Dorn R, Reuter G (2003a) Position-effect variegation and the genetic dissection of chromatin regulation in Drosophila. Semin Cell Dev Biol 14:67–75

    PubMed  CAS  Google Scholar 

  • Schotta G, Ebert A, Reuter G (2003b) SU(VAR)3-9 is a conserved key function in heterochromatic gene silencing. Genetica 117:149–158

    PubMed  CAS  Google Scholar 

  • Schramke V, Allshire R (2004) Those interfering little RNAs! Silencing and eliminating chromatin. Curr Opin Genet Dev 14:174–180

    PubMed  CAS  Google Scholar 

  • Semeshin F, Belyaeva S, Zhimulev F (2001) Electron microscope mapping of the pericentric and intercalary heterochromatic regions of the polytene chromosomes of the mutant Suppressor of underreplication in Drosophila melanogaster. Chromosoma 110:487–500

    PubMed  CAS  Google Scholar 

  • Shareef MM, King C, Damaj M, Badagu R, Huang DW, 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

    PubMed  CAS  Google Scholar 

  • Shibahara K, Stillman B (1999) Replication-dependent marking of DNA by PCNA facilitates CAF-1-coupled inheritance of chromatin. Cell 96:575–585

    PubMed  CAS  Google Scholar 

  • Smith AV, Orr-Weaver TL (1991) The regulation of the cell cycle during Drosophila embryogenesis: the transition to polyteny. Development 112:997–1008

    PubMed  CAS  Google Scholar 

  • Sun FL, Cuaycong MH, Elgin SC (2001) Long-range nucleosome ordering is associated with gene silencing in Drosophila melanogaster pericentric heterochromatin. Mol Cell Biol 21:2867–2879

    PubMed  CAS  Google Scholar 

  • Taddei A, Roche D, Sibarita JB, Turner BM, Almouzni G (1999) Duplication and maintenance of heterochromatin domains. J Cell Biol 147:1153–1166

    PubMed  CAS  Google Scholar 

  • Tagami H, Ray-Gallet D, Almouzni G, Nakatani Y (2004) Histone H3.1 and H3.3 complexes mediate nucleosome assembly pathways dependent or independent of DNA synthesis. Cell 116:51–61

    PubMed  CAS  Google Scholar 

  • Tatematsu KI, Yamazaki T, Ishikawa F (2000) MBD2–MBD3 complex binds to hemi-methylated DNA and forms a complex containing DNMT1 at the replication foci in late S phase. Genes Cells 5:677–688

    PubMed  CAS  Google Scholar 

  • Tchurikov NA, Kretova OV, Chernov BK, Golova YB, Zhimulev IF, Zykov IA (2004) SuUR protein binds to the boundary regions separating forum domains in Drosophila melanogaster. J Biol Chem 279:11705–11710

    PubMed  CAS  Google Scholar 

  • Triolo T, Sternglanz R (1996) Role of interactions between the origin recognition complex and SIR1 in transcriptional silencing. Nature 381:251–253

    PubMed  CAS  Google Scholar 

  • Verdel A, Jia S, Gerber S, Sugiyama T, Gygi S, Grewal SI, Moazed D (2004) RNAi-mediated targeting of heterochromatin by the RITS complex. Science 303:672–676

    PubMed  CAS  Google Scholar 

  • Verschure PJ, van der Kraan I, de Leeuw W, van der Vlag J, Carpenter AE, Belmont, AS, van Driel R (2005) In vivo HP1 targetting causes large-scale chromatin condensation and enhanced histone lysine methylation. Mol Cell Biol 25:4552–4564

    PubMed  CAS  Google Scholar 

  • Vertino PM, Sekowski JA, Coll JM, Applegren N, Han S, Hickey RJ, Malkas LH (2002) DNMT1 is a component of a multiprotein DNA replication complex. Cell Cycle 1:416–423

    PubMed  CAS  Google Scholar 

  • Volkova EI, Yurlova AA, Kolesnikova TD, Makunin IV, Zhimulev IF (2003) Ectopic expression of the Suppressor of Underreplication gene inhibits endocycles but not the mitotic cell cycle in Drosophila melanogaster. Mol Genet Genomics 270:387–393

    PubMed  CAS  Google Scholar 

  • Volpe TA, Kidner C, Hall IM, Teng G, Grewal SIS, Martienssen RA (2002) Regulation of heterochormatic silencing and histone H3 lysine-9 methylation by RNAi. Science 297:1833–1837

    PubMed  CAS  Google Scholar 

  • Wade PA (2001) Methyl CpG-binding proteins and transcriptional repression. Bioessays 23:1131–1137

    PubMed  CAS  Google Scholar 

  • Wakimoto BT, Hearn MG (1990) The effects of chromosome rearrangements on the expression of heterochromatic genes in chromosome 2L of Drosophila melanogaster. Genetics 125:141–154

    PubMed  CAS  Google Scholar 

  • Wallrath LL, Elgin SC (1995) Position effect variegation in Drosophila is associated with an altered chromatin structure. Genes Dev 9:1263–1277

    PubMed  CAS  Google Scholar 

  • Zhang Z, Shibahara K, Stillman B (2000) PCNA connects DNA replication to epigenetic inheritance in yeast. Nature 408:221–225

    PubMed  CAS  Google Scholar 

  • Zhimulev IF, Belyaeva ES (2003) Intercalary heterochromatin and genetic silencing. BioEssays 25:1040–1051

    PubMed  CAS  Google Scholar 

  • Zhimulev IF, Belyaeva ES, Makunin IV, Pirrotta V, Volkova EI, Alekseyenko AA, Andreyeva EN, Makarevich GF, Boldyreva LV, Nanayev RA, Demakova OV (2003a) Influence of the SuUR gene on intercalary heterochromatin in Drosophila melanogaster polytene chromosomes. Chromosoma 111:377–398

    PubMed  CAS  Google Scholar 

  • Zhimulev IF, Belyaeva ES, Semeshin VF, Shloma VV, Makunin IV, Volkova EI (2003b) Overexpression of the SuUR gene induces reversible modifications at pericentric, telomeric and intercalary heterochromatin of Drosophila melanogaster polytene chromosomes. J Cell Sci 116:169–176

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank A. Aslanian, S. Bell, H. Blitzblau, S. Bumgarner, J. Pesin, and E. Rogakou for helpful comments on the manuscript. We are grateful to I. Zhimulev for permission to reproduce the micrographs in Fig. 2. The authors were supported by grants from the NIH (GM57541) and the Harold G. and Leila Y. Mathers Charitable Foundation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Terry L. Orr-Weaver.

Additional information

Communicated by E.A. Nigg.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wallace, J.A., Orr-Weaver, T.L. Replication of heterochromatin: insights into mechanisms of epigenetic inheritance. Chromosoma 114, 389–402 (2005). https://doi.org/10.1007/s00412-005-0024-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00412-005-0024-6

Keywords

Navigation