Advertisement

Heterochromatin: A Critical Part of the Genome

  • Lori L. Wallrath
  • Michael W. Vitalini
  • Sarah C. R. Elgin
Chapter

Abstract

Heterochromatin represents highly condensed portions of the genome that are located near centromeres and telomeres of chromosomes. Once thought to be merely “junk DNA”, heterochromatin is now recognized as an important part of the genome that possesses many functions. Heterochromatin is distinguished from the gene-rich euchromatin by a high concentration of repetitive DNA sequences, including transposons and is marked by specific histone posttranslational modifications and distinct nonhistone chromosomal proteins. Heterochromatin is required for proper chromosome segregation and maintenance of silencing. Loss of heterochromatin leads to the inappropriate activation of genes, including transposable elements, which contribute to genomic instability in diseases such as cancer.

Keywords

Transposable Element Nuclear Envelope Constitutive Heterochromatin Heterochromatin Formation Pericentric Heterochromatin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

bp

Base pairs

CLRC

Clr4-Rik1-Cul4 complex

DNA

Deoxyribonucleic acid

dsRNA

Double-stranded RNA

E(var)

Enhancer of variegation

FISH

Fluorescence in situ hybridization

H3K4me

Methylated lysine 4 of histone H3

H3K9me

Methylated lysine 9 of histone H3

HP1a

Heterochromatin protein 1a

HS

DNase I hypersensitive site

IGF2

Insulin-like growth factor 2

LADs

Lamin-associated domains

LBR

Lamin B receptor

PEV

Position effect variegation

piRNA

Piwi-interacting RNA

RITS

RNA-induced transcriptional silencing complex

RNA

Ribonucleic acid

rRNA

Ribosomal RNA

siRNA

Short interfering RNA

Su(var)

Suppressor of variegation

Swi6

Switch 6, an HPla homologue

References

  1. Ashe A, Sapetschnig A, Weick EM, Mitchell J, Bagijn MP et al (2012) piRNAs can trigger a multigenerational epigenetic memory in the germline of C. elegans. Cell 150:88–99PubMedGoogle Scholar
  2. Aulner N, Monod C, Mandicourt G, Jullien D, Cuvier O et al (2002) The AT-hook protein D1 is essential for Drosophila melanogaster development and is implicated in position-effect variegation. Mol Cell Biol 22:1218–1232PubMedGoogle Scholar
  3. Aygun O, Grewal SI (2010) Assembly and functions of heterochromatin in the fission yeast genome. Cold Spring Harb Symp Quant Biol 75:259–267PubMedGoogle Scholar
  4. Bancaud A, Huet S, Daigle N, Mozziconacci J, Beaudouin J et al (2009) Molecular crowding affects diffusion and binding of nuclear proteins in heterochromatin and reveals the fractal organization of chromatin. EMBO J 28:3785–3798PubMedGoogle Scholar
  5. Bannister AJ, Zegerman P, Partridge JF, Miska EA, Thomas JO et al (2001) Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature 410:120–124PubMedGoogle Scholar
  6. Bergman Y, Cedar H (2013) DNA methylation dynamics in health and disease. Nat Struct Mol Biol 20:274–281PubMedGoogle Scholar
  7. Bernard P, Allshire R (2002) Centromeres become unstuck without heterochromatin. Trends Cell Biol 12:419–424PubMedGoogle Scholar
  8. Bernstein BE, Liu CL, Humphrey EL, Perlstein EO, Schreiber SL (2004) Global nucleosome occupancy in yeast. Genome Biol 5:R62PubMedGoogle Scholar
  9. Blattes R, Monod C, Susbielle G, Cuvier O, Wu JH et al (2006) Displacement of D1, HP1 and topoisomerase II from satellite heterochromatin by a specific polyamide. EMBO J 25:2397–2408PubMedGoogle Scholar
  10. Brogaard K, Xi L, Wang JP, Widom J (2012) A map of nucleosome positions in yeast at base-pair resolution. Nature 486:496–501PubMedGoogle Scholar
  11. Bucksch M, Ziegler M, Kosayakova N, Mulatinho MV, Llerena JC Jr et al (2012) A new multicolor fluorescence in situ hybridization probe set directed against human heterochromatin: HCM-FISH. J Histochem Cytochem 60:530–536PubMedGoogle Scholar
  12. Buhler M, Moazed D (2007) Transcription and RNAi in heterochromatic gene silencing. Nat Struct Mol Biol 14:1041–1048PubMedGoogle Scholar
  13. Bulut-Karslioglu A, Perrera V, Scaranaro M, de la Rosa-Velazquez IA, van de Nobelen S et al (2012) A transcription factor-based mechanism for mouse heterochromatin formation. Nat Struct Mol Biol 19:1023–1030PubMedGoogle Scholar
  14. Carone DM, Lawrence JB (2012) Heterochromatin instability in cancer: from the Barr body to satellites and the nuclear periphery. Semin Cancer Biol 23(2):99–108PubMedGoogle Scholar
  15. Castel SE, Martienssen RA (2013) RNA interference in the nucleus: roles for small RNAs in transcription, epigenetics and beyond. Nat Rev Genet 14:100–112PubMedGoogle Scholar
  16. Cenci G, Ciapponi L, Gatti M (2005) The mechanism of telomere protection: a comparison between Drosophila and humans. Chromosoma 114:135–145PubMedGoogle Scholar
  17. Chao W, Huynh KD, Spencer RJ, Davidow LS, Lee JT (2002) CTCF, a candidate trans-acting factor for X-inactivation choice. Science 295:345–347PubMedGoogle Scholar
  18. Chen WY, Townes TM (2000) Molecular mechanism for silencing virally transduced genes involves histone deacetylation and chromatin condensation. Proc Natl Acad Sci USA 97:377–382PubMedGoogle Scholar
  19. Chiolo I, Minoda A, Colmenares SU, Polyzos A, Costes SV et al (2011) Double-strand breaks in heterochromatin move outside of a dynamic HP1a domain to complete recombinational repair. Cell 144:732–744PubMedGoogle Scholar
  20. Chu L, Zhu T, Liu X, Yu R, Bacanamwo M et al (2012) SUV39H1 orchestrates temporal dynamics of centromeric methylation essential for faithful chromosome segregation in mitosis. J Mol Cell Biol 4:331–340PubMedGoogle Scholar
  21. Costa-Nunes P, Pontes O, Preuss SB, Pikaard CS (2010) Extra views on RNA-dependent DNA methylation and MBD6-dependent heterochromatin formation in nucleolar dominance. Nucleus 1:254–259PubMedGoogle Scholar
  22. Creamer KM, Partridge JF (2011) RITS-connecting transcription, RNA interference, and heterochromatin assembly in fission yeast. Wiley Interdiscip Rev RNA 2:632–646PubMedGoogle Scholar
  23. Cremer T, Cremer M (2010) Chromosome territories. Cold Spring Harb Perspect Biol 2:a003889PubMedGoogle Scholar
  24. Croft JA, Bridger JM, Boyle S, Perry P, Teague P et al (1999) Differences in the localization and morphology of chromosomes in the human nucleus. J Cell Biol 145:1119–1131PubMedGoogle Scholar
  25. Cryderman DE, Cuaycong MH, Elgin SC, Wallrath LL (1998) Characterization of sequences associated with position-effect variegation at pericentric sites in Drosophila heterochromatin. Chromosoma 107:277–285PubMedGoogle Scholar
  26. Cryderman DE, Tang H, Bell C, Gilmour DS, Wallrath LL (1999) Heterochromatic silencing of Drosophila heat shock genes acts at the level of promoter potentiation. Nucleic Acids Res 27:3364–3370PubMedGoogle Scholar
  27. Czermin B, Schotta G, Hulsmann BB, Brehm A, Becker PB et al (2001) Physical and functional association of SU(VAR)3-9 and HDAC1 in Drosophila. EMBO Rep 2:915–919PubMedGoogle Scholar
  28. Danzer JR, Wallrath LL (2004) Mechanisms of HP1-mediated gene silencing in Drosophila. Development 131:3571–3580PubMedGoogle Scholar
  29. de Lange T (2010) How shelterin solves the telomere end-protection problem. Cold Spring Harb Symp Quant Biol 75:167–177PubMedGoogle Scholar
  30. Dernburg AF, Sedat JW (1998) Mapping three-dimensional chromosome architecture in situ. Methods Cell Biol 53:187–233PubMedGoogle Scholar
  31. Dernburg AF, Sedat JW, Hawley RS (1996) Direct evidence of a role for heterochromatin in meiotic chromosome segregation. Cell 86:135–146PubMedGoogle Scholar
  32. Dialynas G, Speese S, Budnik V, Geyer PK, Wallrath LL (2010) The role of Drosophila Lamin C in muscle function and gene expression. Development 137:3067–3077PubMedGoogle Scholar
  33. Donaldson KM, Lui A, Karpen GH (2002) Modifiers of terminal deficiency-associated position effect variegation in Drosophila. Genetics 160:995–1009PubMedGoogle Scholar
  34. Dorer DR, Henikoff S (1994) Expansions of transgene repeats cause heterochromatin formation and gene silencing in Drosophila. Cell 77:993–1002PubMedGoogle Scholar
  35. Dorn R, Szidonya J, Korge G, Sehnert M, Taubert H et al (1993) P transposon-induced dominant enhancer mutations of position-effect variegation in Drosophila melanogaster. Genetics 133:279–290PubMedGoogle Scholar
  36. Eissenberg JC, Morris GD, Reuter G, Hartnett T (1992) The heterochromatin-associated protein HP-1 is an essential protein in Drosophila with dosage-dependent effects on position-effect variegation. Genetics 131:345–352PubMedGoogle Scholar
  37. Elgin SC, Grewal SI (2003) Heterochromatin: silence is golden. Curr Biol 13:R895–R898PubMedGoogle Scholar
  38. Eltsov M, Maclellan KM, Maeshima K, Frangakis AS, Dubochet J (2008) Analysis of cryo-electron microscopy images does not support the existence of 30-nm chromatin fibers in mitotic chromosomes in situ. Proc Natl Acad Sci USA 105:19732–19737PubMedGoogle Scholar
  39. Fahy J, Jeltsch A, Arimondo PB (2012) DNA methyltransferase inhibitors in cancer: a chemical and therapeutic patent overview and selected clinical studies. Expert Opin Ther Pat 22:1427–1442PubMedGoogle Scholar
  40. Finlan LE, Sproul D, Thomson I, Boyle S, Kerr E et al (2008) Recruitment to the nuclear periphery can alter expression of genes in human cells. PLoS Genet 4:e1000039PubMedGoogle Scholar
  41. Fuks F, Hurd PJ, Deplus R, Kouzarides T (2003) The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase. Nucleic Acids Res 31:2305–2312PubMedGoogle Scholar
  42. Fussner E, Ching RW, Bazett-Jones DP (2011) Living without 30nm chromatin fibers. Trends Biochem Sci 36:1–6PubMedGoogle Scholar
  43. Gaffney DJ, McVicker G, Pai AA, Fondufe-Mittendorf YN, Lewellen N et al (2012) Controls of nucleosome positioning in the human genome. PLoS Genet 8:e1003036PubMedGoogle Scholar
  44. Ghirlando RFG (2013) Chromatin structure outside and inside the nucleus. Biopolymers 99:225–232PubMedGoogle Scholar
  45. Girton JR, Johansen KM (2008) Chromatin structure and the regulation of gene expression: the lessons of PEV in Drosophila. Adv Genet 61:1–43PubMedGoogle Scholar
  46. Hager GL, Nagaich AK, Johnson TA, Walker DA, John S (2004) Dynamics of nuclear receptor movement and transcription. Biochim Biophys Acta 1677:46–51PubMedGoogle Scholar
  47. Haldar S, Saini A, Nanda JS, Saini S, Singh J (2011) Role of Swi6/HP1 self-association-mediated recruitment of Clr4/Suv39 in establishment and maintenance of heterochromatin in fission yeast. J Biol Chem 286:9308–9320PubMedGoogle Scholar
  48. Hathaway NA, Bell O, Hodges C, Miller EL, Neel DS et al (2012) Dynamics and memory of heterochromatin in living cells. Cell 149:1447–1460PubMedGoogle Scholar
  49. Hayden KE, Strome ED, Merrett SL, Lee HR, Rudd MK et al (2013) Sequences associated with centromere competency in the human genome. Mol Cell Biol 33:763–772PubMedGoogle Scholar
  50. Heitz E (1928) Das heterochromatin der moose. Jahrb Wiss Bot 69:726–818Google Scholar
  51. Hiragami-Hamada K, Xie SQ, Saveliev A, Uribe-Lewis S, Pombo A et al (2009) The molecular basis for stability of heterochromatin-mediated silencing in mammals. Epigenetics Chromatin 2:14PubMedGoogle Scholar
  52. Honda S, Lewis ZA, Shimada K, Fischle W, Sack R et al (2012) Heterochromatin protein 1 forms distinct complexes to direct histone deacetylation and DNA methylation. Nat Struct Mol Biol 19:471–477, S471PubMedGoogle Scholar
  53. Huang XA, Yin H, Sweeney S, Raha D, Snyder M et al (2013) A major epigenetic programming mechanism guided by piRNAs. Dev Cell 24:502–516PubMedGoogle Scholar
  54. Jacobs SA, Taverna SD, Zhang Y, Briggs SD, Li J et al (2001) Specificity of the HP1 chromo domain for the methylated N-terminus of histone H3. EMBO J 20:5232–5241PubMedGoogle Scholar
  55. James TC, Eissenberg JC, Craig C, Dietrich V, Hobson A et al (1989) Distribution patterns of HP1, a heterochromatin-associated nonhistone chromosomal protein of Drosophila. Eur J Cell Biol 50:170–180PubMedGoogle Scholar
  56. Javerzat JP, McGurk G, Cranston G, Barreau C, Bernard P et al (1999) Defects in components of the proteasome enhance transcriptional silencing at fission yeast centromeres and impair chromosome segregation. Mol Cell Biol 19:5155–5165PubMedGoogle Scholar
  57. Jenuwein T, Allis CD (2001) Translating the histone code. Science 293:1074–1080PubMedGoogle Scholar
  58. Joshi AA, Struhl K (2005) Eaf3 chromodomain interaction with methylated H3-K36 links histone deacetylation to Pol II elongation. Mol Cell 20:971–978PubMedGoogle Scholar
  59. Joti Y, Hikima T, Nishino Y, Kamada F, Hihara S et al (2012) Chromosomes without a 30-nm chromatin fiber. Nucleus 3:404–410PubMedGoogle Scholar
  60. Kaeberlein M, McVey M, Guarente L (1999) The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev 13:2570–2580PubMedGoogle Scholar
  61. Kamakaka RT, Rine J (1998) Sir- and silencer-independent disruption of silencing in Saccharomyces by Sas10p. Genetics 149:903–914PubMedGoogle Scholar
  62. Kharchenko PV, Alekseyenko AA, Schwartz YB, Minoda A, Riddle NC et al (2011) Comprehensive analysis of the chromatin landscape in Drosophila melanogaster. Nature 471:480–485PubMedGoogle Scholar
  63. Kind J, Pagie L, Ortabozkoyun H, Boyle S, de Vries SS et al (2013) Single-cell dynamics of genome-nuclear lamina interactions. Cell 153:178–192PubMedGoogle Scholar
  64. Kitada T, Kuryan BG, Tran NN, Song C, Xue Y et al (2012) Mechanism for epigenetic variegation of gene expression at yeast telomeric heterochromatin. Genes Dev 26:2443–2455PubMedGoogle Scholar
  65. Klenov MS, Lavrov SA, Stolyarenko AD, Ryazansky SS, Aravin AA et al (2007) Repeat-associated siRNAs cause chromatin silencing of retrotransposons in the Drosophila melanogaster germline. Nucleic Acids Res 35:5430–5438PubMedGoogle Scholar
  66. Knight S, Zhang F, Mueller-Kuller U, Bokhoven M, Gupta A et al (2012) Safer, silencing-resistant lentiviral vectors: optimization of the ubiquitous chromatin-opening element through elimination of aberrant splicing. J Virol 86:9088–9095PubMedGoogle Scholar
  67. Kolbl AC, Weigl D, Mulaw M, Thormeyer T, Bohlander SK et al (2012) The radial nuclear positioning of genes correlates with features of megabase-sized chromatin domains. Chromosome Res 20:735–752PubMedGoogle Scholar
  68. Kumaran RI, Spector DL (2008) A genetic locus targeted to the nuclear periphery in living cells maintains its transcriptional competence. J Cell Biol 180:51–65PubMedGoogle Scholar
  69. Kumari D, Usdin K (2010) The distribution of repressive histone modifications on silenced FMR1 alleles provides clues to the mechanism of gene silencing in fragile X syndrome. Hum Mol Genet 19:4634–4642PubMedGoogle Scholar
  70. Kurzhals RL, Titen SW, Xie HB, Golic KG (2011) Chk2 and p53 are haploinsufficient with dependent and independent functions to eliminate cells after telomere loss. PLoS Genet 7:e1002103PubMedGoogle Scholar
  71. 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 410:116–120PubMedGoogle Scholar
  72. Le Thomas A, Rogers AK, Webster A, Marinov GK, Liao SE et al (2013) Piwi induces piRNA-guided transcriptional silencing and establishment of a repressive chromatin state. Genes Dev 27:390–399PubMedGoogle Scholar
  73. Lechner M, Marz M, Ihling C, Sinz A, Stadler PF et al (2013) The correlation of genome size and DNA methylation rate in metazoans. Theory Biosci 132:47–60PubMedGoogle Scholar
  74. Lee TF, Gurazada SG, Zhai J, Li S, Simon SA et al (2012) RNA polymerase V-dependent small RNAs in Arabidopsis originate from small, intergenic loci including most SINE repeats. RNA Biol 9:1031Google Scholar
  75. Lefrancois P, Auerbach RK, Yellman CM, Roeder GS, Snyder M (2013) Centromere-like regions in the budding yeast genome. PLoS Genet 9:e1003209PubMedGoogle Scholar
  76. Li Y, Danzer JR, Alvarez P, Belmont AS, Wallrath LL (2003) Effects of tethering HP1 to euchromatic regions of the Drosophila genome. Development 130:1817–1824PubMedGoogle Scholar
  77. Locke J, Kotarski MA, Tartof KD (1988) Dosage-dependent modifiers of position effect variegation in Drosophila and a mass action model that explains their effect. Genetics 120:181–198PubMedGoogle Scholar
  78. Mahy NL, Perry PE, Bickmore WA (2002) Gene density and transcription influence the localization of chromatin outside of chromosome territories detectable by FISH. J Cell Biol 159:753–763PubMedGoogle Scholar
  79. Marshall WF, Sedat JW (1999) Nuclear architecture. Results Probl Cell Differ 25:283–301PubMedGoogle Scholar
  80. Matzke MA, Mette MF, Matzke AJ (2000) Transgene silencing by the host genome defense: implications for the evolution of epigenetic control mechanisms in plants and vertebrates. Plant Mol Biol 43:401–415PubMedGoogle Scholar
  81. McCue AD, Slotkin RK (2012) Transposable element small RNAs as regulators of gene expression. Trends Genet 28:616–623PubMedGoogle Scholar
  82. Meaburn KJ, Misteli T, Soutoglou E (2007) Spatial genome organization in the formation of chromosomal translocations. Semin Cancer Biol 17:80–90PubMedGoogle Scholar
  83. Meister P, Taddei A (2013) Building silent compartments at the nuclear periphery: a recurrent theme. Curr Opin Genet Dev 23(2):96–103PubMedGoogle Scholar
  84. Mermoud JE, Rowbotham SP, Varga-Weisz PD (2011) Keeping chromatin quiet: how nucleosome remodeling restores heterochromatin after replication. Cell Cycle 10:4017–4025PubMedGoogle Scholar
  85. Meuleman W, Peric-Hupkes D, Kind J, Beaudry JB, Pagie L et al (2013) Constitutive nuclear lamina-genome interactions are highly conserved and associated with A/T-rich sequence. Genome Res 23:270–280PubMedGoogle Scholar
  86. Mewborn SK, Lese Martin C, Ledbetter DH (2005) The dynamic nature and evolutionary history of subtelomeric and pericentromeric regions. Cytogenet Genome Res 108:22–25PubMedGoogle Scholar
  87. Muller H (1930) Types of visible variations induced by X-rays in Drosophila. J Genet 22:299–334Google Scholar
  88. Musselman CA, Lalonde ME, Cote J, Kutateladze TG (2012) Perceiving the epigenetic landscape through histone readers. Nat Struct Mol Biol 19:1218–1227PubMedGoogle Scholar
  89. Nishino Y, Eltsov M, Joti Y, Ito K, Takata H et al (2012) Human mitotic chromosomes consist predominantly of irregularly folded nucleosome fibres without a 30-nm chromatin structure. EMBO J 31:1644–1653PubMedGoogle Scholar
  90. Pageau GJ, Lawrence JB (2006) BRCA1 foci in normal S-phase nuclei are linked to interphase centromeres and replication of pericentric heterochromatin. J Cell Biol 175:693–701PubMedGoogle Scholar
  91. Peng JC, Karpen GH (2008) Epigenetic regulation of heterochromatic DNA stability. Curr Opin Genet Dev 18:204–211PubMedGoogle Scholar
  92. Peng JC, Lin H (2013) Beyond transposons: the epigenetic and somatic functions of the Piwi-piRNA mechanism. Curr Opin Cell Biol 25(2):190–194PubMedGoogle Scholar
  93. Pfeifer GP, Tanguay RL, Steigerwald SD, Riggs AD (1990) In vivo footprint and methylation analysis by PCR-aided genomic sequencing: comparison of active and inactive X chromosomal DNA at the CpG island and promoter of human PGK-1. Genes Dev 4:1277–1287PubMedGoogle Scholar
  94. Rabl C (1885) Uber Zelltheilung. Morphologisches Jahrbuch, pp 214–330Google Scholar
  95. Reddy KL, Zullo JM, Bertolino E, Singh H (2008) Transcriptional repression mediated by repositioning of genes to the nuclear lamina. Nature 452:243–247PubMedGoogle Scholar
  96. Riddle NC, Jung YL, Gu T, Alekseyenko AA, Asker D et al (2012) Enrichment of HP1a on Drosophila chromosome 4 genes creates an alternate chromatin structure critical for regulation in this heterochromatic domain. PLoS Genet 8:e1002954PubMedGoogle Scholar
  97. Rong YS (2008) Telomere capping in Drosophila: dealing with chromosome ends that most resemble DNA breaks. Chromosoma 117:235–242PubMedGoogle Scholar
  98. Rozhkov NV, Hammell M, Hannon GJ (2013) Multiple roles for Piwi in silencing Drosophila transposons. Genes Dev 27:400–412PubMedGoogle Scholar
  99. Sackton TB, Hartl DL (2013) Meta-analysis reveals that genes regulated by the Y chromosome in Drosophila melanogaster are preferentially localized to repressive chromatin. Genome Biol Evol 5:255–266PubMedGoogle Scholar
  100. Saunders WS, Chue C, Goebl M, Craig C, Clark RF et al (1993) Molecular cloning of a human homologue of Drosophila heterochromatin protein HP1 using anti-centromere autoantibodies with anti-chromo specificity. J Cell Sci 104(Pt 2):573–582PubMedGoogle Scholar
  101. Sawarkar R, Paro R (2010) Interpretation of developmental signaling at chromatin: the Polycomb perspective. Dev Cell 19:651–661PubMedGoogle Scholar
  102. Schneiderman JI, Goldstein S, Ahmad K (2010) Perturbation analysis of heterochromatin-mediated gene silencing and somatic inheritance. PLoS Genet 6(9):e1001095PubMedGoogle Scholar
  103. Schotta G, Ebert A, Dorn R, Reuter G (2003) Position-effect variegation and the genetic dissection of chromatin regulation in Drosophila. Semin Cell Dev Biol 14:67–75PubMedGoogle Scholar
  104. Schultz J (1936) Variegation in Drosophila and the inert chromosome regions. Proc Natl Acad Sci USA 22:27–33PubMedGoogle Scholar
  105. Seum C, Spierer A, Delattre M, Pauli D, Spierer P (2000) A GAL4-HP1 fusion protein targeted near heterochromatin promotes gene silencing. Chromosoma 109:453–459PubMedGoogle Scholar
  106. Shirayama M, Seth M, Lee HC, Gu W, Ishidate T et al (2012) piRNAs initiate an epigenetic memory of nonself RNA in the C. elegans germline. Cell 150:65–77PubMedGoogle Scholar
  107. Smallwood A, Esteve PO, Pradhan S, Carey M (2007) Functional cooperation between HP1 and DNMT1 mediates gene silencing. Genes Dev 21:1169–1178PubMedGoogle Scholar
  108. Solovei I, Kreysing M, Lanctot C, Kosem S, Peichl L et al (2009) Nuclear architecture of rod photoreceptor cells adapts to vision in mammalian evolution. Cell 137:356–368PubMedGoogle Scholar
  109. Solovei I, Wang AS, Thanisch K, Schmidt CS, Krebs S et al (2013) LBR and lamin A/C sequentially tether peripheral heterochromatin and inversely regulate differentiation. Cell 152:584–598PubMedGoogle Scholar
  110. Soubry A, Schildkraut JM, Murtha A, Wang F, Huang Z et al (2013) Paternal obesity is associated with IGF2 hypomethylation in newborns: results from a Newborn Epigenetics Study (NEST) cohort. BMC Med 11:29PubMedGoogle Scholar
  111. Stewart MD, Li J, Wong J (2005) Relationship between histone H3 lysine 9 methylation, transcription repression, and heterochromatin protein 1 recruitment. Mol Cell Biol 25:2525–2538PubMedGoogle Scholar
  112. Sun FL, Cuaycong MH, Elgin SC (2001) Long-range nucleosome ordering is associated with gene silencing in Drosophila melanogaster pericentric heterochromatin. Mol Cell Biol 21:2867–2879PubMedGoogle Scholar
  113. Sun X, Le HD, Wahlstrom JM, Karpen GH (2003) Sequence analysis of a functional Drosophila centromere. Genome Res 13:182–194PubMedGoogle Scholar
  114. Sun B, Hong J, Zhang P, Dong X, Shen X et al (2008) Molecular basis of the interaction of Saccharomyces cerevisiae Eaf3 chromo domain with methylated H3K36. J Biol Chem 283:36504–36512PubMedGoogle Scholar
  115. Sussel L, Vannier D, Shore D (1993) Epigenetic switching of transcriptional states: cis- and trans-acting factors affecting establishment of silencing at the HMR locus in Saccharomyces cerevisiae. Mol Cell Biol 13:3919–3928PubMedGoogle Scholar
  116. Towbin BD, Gonzalez-Aguilera C, Sack R, Gaidatzis D, Kalck V et al (2012) Step-wise methylation of histone H3K9 positions heterochromatin at the nuclear periphery. Cell 150:934–947PubMedGoogle Scholar
  117. Tschiersch B, Hofmann A, Krauss V, Dorn R, Korge G et al (1994) The protein encoded by the Drosophila position-effect variegation suppressor gene Su(var)3-9 combines domains of antagonistic regulators of homeotic gene complexes. EMBO J 13:3822–3831PubMedGoogle Scholar
  118. van der Vlag J, den Blaauwen JL, Sewalt RG, van Driel R, Otte AP (2000) Transcriptional repression mediated by polycomb group proteins and other chromatin-associated repressors is selectively blocked by insulators. J Biol Chem 275:697–704PubMedGoogle Scholar
  119. van Steensel B (2011) Chromatin: constructing the big picture. EMBO J 30:1885–1895PubMedGoogle Scholar
  120. Verdel A, Vavasseur A, Le Gorrec M, Touat-Todeschini L (2009) Common themes in siRNA-mediated epigenetic silencing pathways. Int J Dev Biol 53:245–257PubMedGoogle Scholar
  121. Verschure PJ, van der Kraan I, de Leeuw W, van der Vlag J, Carpenter AE et al (2005) In vivo HP1 targeting causes large-scale chromatin condensation and enhanced histone lysine methylation. Mol Cell Biol 25:4552–4564PubMedGoogle Scholar
  122. Wallrath LL, Elgin SC (1995) Position effect variegation in Drosophila is associated with an altered chromatin structure. Genes Dev 9:1263–1277PubMedGoogle Scholar
  123. Wallrath LL, Elgin SC (2012) Enforcing silencing: dynamic HP1 complexes in Neurospora. Nat Struct Mol Biol 19:465–467PubMedGoogle Scholar
  124. Wang SH, Elgin SC (2011) Drosophila Piwi functions downstream of piRNA production mediating a chromatin-based transposon silencing mechanism in female germ line. Proc Natl Acad Sci USA 108:21164–21169PubMedGoogle Scholar
  125. Wang CT, Ho CH, Hseu MJ, Chen CM (2010) The subtelomeric region of the Arabidopsis thaliana chromosome IIIR contains potential genes and duplicated fragments from other chromosomes. Plant Mol Biol 74:155–166PubMedGoogle Scholar
  126. Waterland RA, Jirtle RL (2003) Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol 23:5293–5300PubMedGoogle Scholar
  127. Waterland RA, Jirtle RL (2004) Early nutrition, epigenetic changes at transposons and imprinted genes, and enhanced susceptibility to adult chronic diseases. Nutrition 20:63–68PubMedGoogle Scholar
  128. Weiler KS, Wakimoto BT (1995) Heterochromatin and gene expression in Drosophila. Annu Rev Genet 29:577–605PubMedGoogle Scholar
  129. Whitelaw E, Sutherland H, Kearns M, Morgan H, Weaving L et al (2001) Epigenetic effects on transgene expression. Methods Mol Biol 158:351–368PubMedGoogle Scholar
  130. Wilson KL, Berk JM (2010) The nuclear envelope at a glance. J Cell Sci 123:1973–1978PubMedGoogle Scholar
  131. Wu C, Bingham PM, Livak KJ, Holmgren R, Elgin SC (1979) The chromatin structure of specific genes: I. Evidence for higher order domains of defined DNA sequence. Cell 16:797–806PubMedGoogle Scholar
  132. Wustmann G, Szidonya J, Taubert H, Reuter G (1989) The genetics of position-effect variegation modifying loci in Drosophila melanogaster. Mol Gen Genet 217:520–527PubMedGoogle Scholar
  133. Zheng H, Chen L, Pledger WJ, Fang J, Chen J (2013) p53 promotes repair of heterochromatin DNA by regulating JMJD2b and SUV39H1 expression. Oncogene. doi: 10.1038/onc.2013.6Google Scholar
  134. Zhu Q, Pao GM, Huynh AM, Suh H, Tonnu N et al (2011) BRCA1 tumour suppression occurs via heterochromatin-mediated silencing. Nature 477:179–184PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Lori L. Wallrath
    • 1
  • Michael W. Vitalini
    • 2
  • Sarah C. R. Elgin
    • 3
  1. 1.Department of BiochemistryUniversity of IowaIowa CityUSA
  2. 2.Department of BiologySt. Ambrose UniversityDavenportUSA
  3. 3.Department of BiologyWashington University in St. LouisSt. LouisUSA

Personalised recommendations