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Heterochromatin: A Critical Part of the Genome

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Fundamentals of Chromatin

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.

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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

  • 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 150:88–99

    PubMed  CAS  Google Scholar 

  • 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 22:1218–1232

    PubMed  CAS  Google Scholar 

  • Aygun O, Grewal SI (2010) Assembly and functions of heterochromatin in the fission yeast genome. Cold Spring Harb Symp Quant Biol 75:259–267

    PubMed  CAS  Google Scholar 

  • 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 28:3785–3798

    PubMed  CAS  Google Scholar 

  • 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 410:120–124

    PubMed  CAS  Google Scholar 

  • Bergman Y, Cedar H (2013) DNA methylation dynamics in health and disease. Nat Struct Mol Biol 20:274–281

    PubMed  CAS  Google Scholar 

  • Bernard P, Allshire R (2002) Centromeres become unstuck without heterochromatin. Trends Cell Biol 12:419–424

    PubMed  CAS  Google Scholar 

  • Bernstein BE, Liu CL, Humphrey EL, Perlstein EO, Schreiber SL (2004) Global nucleosome occupancy in yeast. Genome Biol 5:R62

    PubMed  Google Scholar 

  • 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 25:2397–2408

    PubMed  CAS  Google Scholar 

  • Brogaard K, Xi L, Wang JP, Widom J (2012) A map of nucleosome positions in yeast at base-pair resolution. Nature 486:496–501

    PubMed  CAS  Google Scholar 

  • 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 60:530–536

    PubMed  CAS  Google Scholar 

  • Buhler M, Moazed D (2007) Transcription and RNAi in heterochromatic gene silencing. Nat Struct Mol Biol 14:1041–1048

    PubMed  Google Scholar 

  • 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 19:1023–1030

    PubMed  CAS  Google Scholar 

  • Carone DM, Lawrence JB (2012) Heterochromatin instability in cancer: from the Barr body to satellites and the nuclear periphery. Semin Cancer Biol 23(2):99–108

    PubMed  Google Scholar 

  • Castel SE, Martienssen RA (2013) RNA interference in the nucleus: roles for small RNAs in transcription, epigenetics and beyond. Nat Rev Genet 14:100–112

    PubMed  CAS  Google Scholar 

  • Cenci G, Ciapponi L, Gatti M (2005) The mechanism of telomere protection: a comparison between Drosophila and humans. Chromosoma 114:135–145

    PubMed  CAS  Google Scholar 

  • Chao W, Huynh KD, Spencer RJ, Davidow LS, Lee JT (2002) CTCF, a candidate trans-acting factor for X-inactivation choice. Science 295:345–347

    PubMed  CAS  Google Scholar 

  • Chen WY, Townes TM (2000) Molecular mechanism for silencing virally transduced genes involves histone deacetylation and chromatin condensation. Proc Natl Acad Sci USA 97:377–382

    PubMed  CAS  Google Scholar 

  • 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 144:732–744

    PubMed  CAS  Google Scholar 

  • 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 4:331–340

    PubMed  CAS  Google Scholar 

  • 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 1:254–259

    PubMed  Google Scholar 

  • Creamer KM, Partridge JF (2011) RITS-connecting transcription, RNA interference, and heterochromatin assembly in fission yeast. Wiley Interdiscip Rev RNA 2:632–646

    PubMed  CAS  Google Scholar 

  • Cremer T, Cremer M (2010) Chromosome territories. Cold Spring Harb Perspect Biol 2:a003889

    PubMed  Google Scholar 

  • 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 145:1119–1131

    PubMed  CAS  Google Scholar 

  • Cryderman DE, Cuaycong MH, Elgin SC, Wallrath LL (1998) Characterization of sequences associated with position-effect variegation at pericentric sites in Drosophila heterochromatin. Chromosoma 107:277–285

    PubMed  CAS  Google Scholar 

  • 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 27:3364–3370

    PubMed  CAS  Google Scholar 

  • 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 2:915–919

    PubMed  CAS  Google Scholar 

  • Danzer JR, Wallrath LL (2004) Mechanisms of HP1-mediated gene silencing in Drosophila. Development 131:3571–3580

    PubMed  CAS  Google Scholar 

  • de Lange T (2010) How shelterin solves the telomere end-protection problem. Cold Spring Harb Symp Quant Biol 75:167–177

    PubMed  Google Scholar 

  • Dernburg AF, Sedat JW (1998) Mapping three-dimensional chromosome architecture in situ. Methods Cell Biol 53:187–233

    PubMed  CAS  Google Scholar 

  • Dernburg AF, Sedat JW, Hawley RS (1996) Direct evidence of a role for heterochromatin in meiotic chromosome segregation. Cell 86:135–146

    PubMed  CAS  Google Scholar 

  • Dialynas G, Speese S, Budnik V, Geyer PK, Wallrath LL (2010) The role of Drosophila Lamin C in muscle function and gene expression. Development 137:3067–3077

    PubMed  CAS  Google Scholar 

  • Donaldson KM, Lui A, Karpen GH (2002) Modifiers of terminal deficiency-associated position effect variegation in Drosophila. Genetics 160:995–1009

    PubMed  CAS  Google Scholar 

  • Dorer DR, Henikoff S (1994) Expansions of transgene repeats cause heterochromatin formation and gene silencing in Drosophila. Cell 77:993–1002

    PubMed  CAS  Google Scholar 

  • 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 133:279–290

    PubMed  CAS  Google Scholar 

  • 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 131:345–352

    PubMed  CAS  Google Scholar 

  • Elgin SC, Grewal SI (2003) Heterochromatin: silence is golden. Curr Biol 13:R895–R898

    PubMed  CAS  Google Scholar 

  • 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 105:19732–19737

    PubMed  CAS  Google Scholar 

  • 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 22:1427–1442

    PubMed  CAS  Google Scholar 

  • 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:e1000039

    PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Fussner E, Ching RW, Bazett-Jones DP (2011) Living without 30nm chromatin fibers. Trends Biochem Sci 36:1–6

    PubMed  CAS  Google Scholar 

  • 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:e1003036

    PubMed  CAS  Google Scholar 

  • Ghirlando RFG (2013) Chromatin structure outside and inside the nucleus. Biopolymers 99:225–232

    PubMed  CAS  Google Scholar 

  • Girton JR, Johansen KM (2008) Chromatin structure and the regulation of gene expression: the lessons of PEV in Drosophila. Adv Genet 61:1–43

    PubMed  CAS  Google Scholar 

  • Hager GL, Nagaich AK, Johnson TA, Walker DA, John S (2004) Dynamics of nuclear receptor movement and transcription. Biochim Biophys Acta 1677:46–51

    PubMed  CAS  Google Scholar 

  • 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 286:9308–9320

    PubMed  CAS  Google Scholar 

  • Hathaway NA, Bell O, Hodges C, Miller EL, Neel DS et al (2012) Dynamics and memory of heterochromatin in living cells. Cell 149:1447–1460

    PubMed  CAS  Google Scholar 

  • 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 33:763–772

    PubMed  CAS  Google Scholar 

  • Heitz E (1928) Das heterochromatin der moose. Jahrb Wiss Bot 69:726–818

    Google Scholar 

  • 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 2:14

    PubMed  Google Scholar 

  • 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, S471

    PubMed  CAS  Google Scholar 

  • Huang XA, Yin H, Sweeney S, Raha D, Snyder M et al (2013) A major epigenetic programming mechanism guided by piRNAs. Dev Cell 24:502–516

    PubMed  CAS  Google Scholar 

  • 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 20:5232–5241

    PubMed  CAS  Google Scholar 

  • 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 50:170–180

    PubMed  CAS  Google Scholar 

  • 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 19:5155–5165

    PubMed  CAS  Google Scholar 

  • Jenuwein T, Allis CD (2001) Translating the histone code. Science 293:1074–1080

    PubMed  CAS  Google Scholar 

  • Joshi AA, Struhl K (2005) Eaf3 chromodomain interaction with methylated H3-K36 links histone deacetylation to Pol II elongation. Mol Cell 20:971–978

    PubMed  CAS  Google Scholar 

  • Joti Y, Hikima T, Nishino Y, Kamada F, Hihara S et al (2012) Chromosomes without a 30-nm chromatin fiber. Nucleus 3:404–410

    PubMed  Google Scholar 

  • 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 13:2570–2580

    PubMed  CAS  Google Scholar 

  • Kamakaka RT, Rine J (1998) Sir- and silencer-independent disruption of silencing in Saccharomyces by Sas10p. Genetics 149:903–914

    PubMed  CAS  Google Scholar 

  • Kharchenko PV, Alekseyenko AA, Schwartz YB, Minoda A, Riddle NC et al (2011) Comprehensive analysis of the chromatin landscape in Drosophila melanogaster. Nature 471:480–485

    PubMed  CAS  Google Scholar 

  • Kind J, Pagie L, Ortabozkoyun H, Boyle S, de Vries SS et al (2013) Single-cell dynamics of genome-nuclear lamina interactions. Cell 153:178–192

    PubMed  CAS  Google Scholar 

  • 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 26:2443–2455

    PubMed  CAS  Google Scholar 

  • 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 35:5430–5438

    PubMed  CAS  Google Scholar 

  • 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 86:9088–9095

    PubMed  CAS  Google Scholar 

  • 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 20:735–752

    PubMed  Google Scholar 

  • Kumaran RI, Spector DL (2008) A genetic locus targeted to the nuclear periphery in living cells maintains its transcriptional competence. J Cell Biol 180:51–65

    PubMed  CAS  Google Scholar 

  • 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 19:4634–4642

    PubMed  CAS  Google Scholar 

  • 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:e1002103

    PubMed  CAS  Google Scholar 

  • 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 

  • 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 27:390–399

    PubMed  Google Scholar 

  • 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 132:47–60

    PubMed  CAS  Google Scholar 

  • 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 9:1031

    CAS  Google Scholar 

  • Lefrancois P, Auerbach RK, Yellman CM, Roeder GS, Snyder M (2013) Centromere-like regions in the budding yeast genome. PLoS Genet 9:e1003209

    PubMed  CAS  Google Scholar 

  • Li Y, Danzer JR, Alvarez P, Belmont AS, Wallrath LL (2003) Effects of tethering HP1 to euchromatic regions of the Drosophila genome. Development 130:1817–1824

    PubMed  CAS  Google Scholar 

  • 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 120:181–198

    PubMed  CAS  Google Scholar 

  • 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 159:753–763

    PubMed  CAS  Google Scholar 

  • Marshall WF, Sedat JW (1999) Nuclear architecture. Results Probl Cell Differ 25:283–301

    PubMed  CAS  Google Scholar 

  • 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 43:401–415

    PubMed  CAS  Google Scholar 

  • McCue AD, Slotkin RK (2012) Transposable element small RNAs as regulators of gene expression. Trends Genet 28:616–623

    PubMed  CAS  Google Scholar 

  • Meaburn KJ, Misteli T, Soutoglou E (2007) Spatial genome organization in the formation of chromosomal translocations. Semin Cancer Biol 17:80–90

    PubMed  CAS  Google Scholar 

  • Meister P, Taddei A (2013) Building silent compartments at the nuclear periphery: a recurrent theme. Curr Opin Genet Dev 23(2):96–103

    PubMed  CAS  Google Scholar 

  • Mermoud JE, Rowbotham SP, Varga-Weisz PD (2011) Keeping chromatin quiet: how nucleosome remodeling restores heterochromatin after replication. Cell Cycle 10:4017–4025

    PubMed  CAS  Google Scholar 

  • 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 23:270–280

    PubMed  CAS  Google Scholar 

  • Mewborn SK, Lese Martin C, Ledbetter DH (2005) The dynamic nature and evolutionary history of subtelomeric and pericentromeric regions. Cytogenet Genome Res 108:22–25

    PubMed  CAS  Google Scholar 

  • Muller H (1930) Types of visible variations induced by X-rays in Drosophila. J Genet 22:299–334

    Google Scholar 

  • Musselman CA, Lalonde ME, Cote J, Kutateladze TG (2012) Perceiving the epigenetic landscape through histone readers. Nat Struct Mol Biol 19:1218–1227

    PubMed  CAS  Google Scholar 

  • 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 31:1644–1653

    PubMed  CAS  Google Scholar 

  • 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 175:693–701

    PubMed  CAS  Google Scholar 

  • Peng JC, Karpen GH (2008) Epigenetic regulation of heterochromatic DNA stability. Curr Opin Genet Dev 18:204–211

    PubMed  CAS  Google Scholar 

  • Peng JC, Lin H (2013) Beyond transposons: the epigenetic and somatic functions of the Piwi-piRNA mechanism. Curr Opin Cell Biol 25(2):190–194

    PubMed  CAS  Google Scholar 

  • 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 4:1277–1287

    PubMed  CAS  Google Scholar 

  • Rabl C (1885) Uber Zelltheilung. Morphologisches Jahrbuch, pp 214–330

    Google Scholar 

  • Reddy KL, Zullo JM, Bertolino E, Singh H (2008) Transcriptional repression mediated by repositioning of genes to the nuclear lamina. Nature 452:243–247

    PubMed  CAS  Google Scholar 

  • 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:e1002954

    PubMed  CAS  Google Scholar 

  • Rong YS (2008) Telomere capping in Drosophila: dealing with chromosome ends that most resemble DNA breaks. Chromosoma 117:235–242

    PubMed  CAS  Google Scholar 

  • Rozhkov NV, Hammell M, Hannon GJ (2013) Multiple roles for Piwi in silencing Drosophila transposons. Genes Dev 27:400–412

    PubMed  CAS  Google Scholar 

  • 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 5:255–266

    PubMed  CAS  Google Scholar 

  • 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):573–582

    PubMed  Google Scholar 

  • Sawarkar R, Paro R (2010) Interpretation of developmental signaling at chromatin: the Polycomb perspective. Dev Cell 19:651–661

    PubMed  CAS  Google Scholar 

  • Schneiderman JI, Goldstein S, Ahmad K (2010) Perturbation analysis of heterochromatin-mediated gene silencing and somatic inheritance. PLoS Genet 6(9):e1001095

    PubMed  Google Scholar 

  • 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 14:67–75

    PubMed  CAS  Google Scholar 

  • Schultz J (1936) Variegation in Drosophila and the inert chromosome regions. Proc Natl Acad Sci USA 22:27–33

    PubMed  CAS  Google Scholar 

  • Seum C, Spierer A, Delattre M, Pauli D, Spierer P (2000) A GAL4-HP1 fusion protein targeted near heterochromatin promotes gene silencing. Chromosoma 109:453–459

    PubMed  CAS  Google Scholar 

  • 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 150:65–77

    PubMed  CAS  Google Scholar 

  • Smallwood A, Esteve PO, Pradhan S, Carey M (2007) Functional cooperation between HP1 and DNMT1 mediates gene silencing. Genes Dev 21:1169–1178

    PubMed  CAS  Google Scholar 

  • 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 137:356–368

    PubMed  CAS  Google Scholar 

  • 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 152:584–598

    PubMed  CAS  Google Scholar 

  • 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 11:29

    PubMed  CAS  Google Scholar 

  • Stewart MD, Li J, Wong J (2005) Relationship between histone H3 lysine 9 methylation, transcription repression, and heterochromatin protein 1 recruitment. Mol Cell Biol 25:2525–2538

    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 

  • Sun X, Le HD, Wahlstrom JM, Karpen GH (2003) Sequence analysis of a functional Drosophila centromere. Genome Res 13:182–194

    PubMed  CAS  Google Scholar 

  • 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 283:36504–36512

    PubMed  CAS  Google Scholar 

  • 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 13:3919–3928

    PubMed  CAS  Google Scholar 

  • 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 150:934–947

    PubMed  CAS  Google Scholar 

  • 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 13:3822–3831

    PubMed  CAS  Google Scholar 

  • 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 275:697–704

    PubMed  Google Scholar 

  • van Steensel B (2011) Chromatin: constructing the big picture. EMBO J 30:1885–1895

    PubMed  Google Scholar 

  • Verdel A, Vavasseur A, Le Gorrec M, Touat-Todeschini L (2009) Common themes in siRNA-mediated epigenetic silencing pathways. Int J Dev Biol 53:245–257

    PubMed  CAS  Google Scholar 

  • 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 25:4552–4564

    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 

  • Wallrath LL, Elgin SC (2012) Enforcing silencing: dynamic HP1 complexes in Neurospora. Nat Struct Mol Biol 19:465–467

    PubMed  CAS  Google Scholar 

  • 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 108:21164–21169

    PubMed  CAS  Google Scholar 

  • 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 74:155–166

    PubMed  CAS  Google Scholar 

  • Waterland RA, Jirtle RL (2003) Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol 23:5293–5300

    PubMed  CAS  Google Scholar 

  • Waterland RA, Jirtle RL (2004) Early nutrition, epigenetic changes at transposons and imprinted genes, and enhanced susceptibility to adult chronic diseases. Nutrition 20:63–68

    PubMed  CAS  Google Scholar 

  • Weiler KS, Wakimoto BT (1995) Heterochromatin and gene expression in Drosophila. Annu Rev Genet 29:577–605

    PubMed  CAS  Google Scholar 

  • Whitelaw E, Sutherland H, Kearns M, Morgan H, Weaving L et al (2001) Epigenetic effects on transgene expression. Methods Mol Biol 158:351–368

    PubMed  CAS  Google Scholar 

  • Wilson KL, Berk JM (2010) The nuclear envelope at a glance. J Cell Sci 123:1973–1978

    PubMed  CAS  Google Scholar 

  • 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 16:797–806

    PubMed  CAS  Google Scholar 

  • Wustmann G, Szidonya J, Taubert H, Reuter G (1989) The genetics of position-effect variegation modifying loci in Drosophila melanogaster. Mol Gen Genet 217:520–527

    PubMed  CAS  Google Scholar 

  • 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.2013.6

    Google Scholar 

  • Zhu Q, Pao GM, Huynh AM, Suh H, Tonnu N et al (2011) BRCA1 tumour suppression occurs via heterochromatin-mediated silencing. Nature 477:179–184

    PubMed  CAS  Google Scholar 

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Correspondence to Lori L. Wallrath .

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Wallrath, L.L., Vitalini, M.W., Elgin, S.C.R. (2014). Heterochromatin: A Critical Part of the Genome. In: Workman, J., Abmayr, S. (eds) Fundamentals of Chromatin. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8624-4_13

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