Skip to main content
Log in

Chromatin at the nuclear periphery and the regulation of genome functions

  • Review
  • Published:
Histochemistry and Cell Biology Aims and scope Submit manuscript

Abstract

Chromatin is not randomly organized in the nucleus, and its spatial organization participates in the regulation of genome functions. However, this spatial organization is also not entirely fixed and modifications of chromatin architecture are implicated in physiological processes such as differentiation or senescence. One of the most striking features of chromatin architecture is the concentration of heterochromatin at the nuclear periphery. A closer examination of the association of chromatin at the nuclear periphery reveals that heterochromatin accumulates at the nuclear lamina, whereas nuclear pores are usually devoid of heterochromatin. After summarizing the current techniques used to study the attachment of chromatin at the nuclear lamina or the nuclear pores, we review the mechanisms underlying these attachments, their plasticity and their consequences on the regulation of gene expression, DNA repair and replication.

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

  • Ahmed K, Dehghani H, Rugg-Gunn P, Fussner E, Rossant J, Bazett-Jones DP (2010) Global chromatin architecture reflects pluripotency and lineage commitment in the early mouse embryo. PLoS One 5:e10531

    PubMed Central  PubMed  Google Scholar 

  • Akhtar A, Gasser SM (2007) The nuclear envelope and transcriptional control. Nat Rev Genet 8:507–517

    CAS  PubMed  Google Scholar 

  • Akhtar W, de Jong J, Pindyurin AV, Pagie L, Meuleman W, de Ridder J, Berns A, Wessels LFA, van Lohuizen M, van Steensel B (2013) Chromatin position effects assayed by thousands of reporters integrated in parallel. Cell 154:914–927

    CAS  PubMed  Google Scholar 

  • Amendola M, van Steensel B (2015) Nuclear lamins are not required for lamina-associated domain organization in mouse embryonic stem cells. EMBO Rep 16:610–617

    CAS  PubMed  Google Scholar 

  • Bai X-T, Gu B-W, Yin T, Niu C, Xi X-D, Zhang J, Chen Z, Chen S-J (2006) Trans-repressive effect of NUP98-PMX1 on PMX1-regulated c-FOS gene through recruitment of histone deacetylase 1 by FG repeats. Cancer Res 66:4584–4590

    CAS  PubMed  Google Scholar 

  • Beliveau BJ, Boettiger AN, Avendaño MS, Jungmann R, McCole RB, Joyce EF, Kim-Kiselak C, Bantignies F, Fonseka CY, Erceg J et al (2015) Single-molecule super-resolution imaging of chromosomes and in situ haplotype visualization using Oligopaint FISH probes. Nat Commun 6:7147

    CAS  PubMed Central  PubMed  Google Scholar 

  • Belmont AS, Zhai Y, Thilenius A (1993) Lamin B distribution and association with peripheral chromatin revealed by optical sectioning and electron microscopy tomography. J Cell Biol 123:1671–1685

    CAS  PubMed  Google Scholar 

  • Bennett CB, Lewis LK, Karthikeyan G, Lobachev KS, Jin YH, Sterling JF, Snipe JR, Resnick MA (2001) Genes required for ionizing radiation resistance in yeast. Nat Genet 29:426–434

    CAS  PubMed  Google Scholar 

  • Bermejo R, Capra T, Jossen R, Colosio A, Frattini C, Carotenuto W, Cocito A, Doksani Y, Klein H, Gómez-González B et al (2011) The replication checkpoint protects fork stability by releasing transcribed genes from nuclear pores. Cell 146:233–246

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bian Q, Khanna N, Alvikas J, Belmont AS (2013) β-Globin cis-elements determine differential nuclear targeting through epigenetic modifications. J Cell Biol 203:767–783

    CAS  PubMed Central  PubMed  Google Scholar 

  • Blasius M, Forment JV, Thakkar N, Wagner SA, Choudhary C, Jackson SP (2011) A phospho-proteomic screen identifies substrates of the checkpoint kinase Chk1. Genome Biol 12:R78

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bolzer A, Kreth G, Solovei I, Koehler D, Saracoglu K, Fauth C, Müller S, Eils R, Cremer C, Speicher MR et al (2005) Three-dimensional maps of all chromosomes in human male fibroblast nuclei and prometaphase rosettes. PLoS Biol 3:e157

    PubMed Central  PubMed  Google Scholar 

  • Boyle S, Gilchrist S, Bridger JM, Mahy NL, Ellis JA, Bickmore WA (2001) The spatial organization of human chromosomes within the nuclei of normal and emerin-mutant cells. Hum Mol Genet 10:211–219

    CAS  PubMed  Google Scholar 

  • Boyle S, Rodesch MJ, Halvensleben HA, Jeddeloh JA, Bickmore WA (2011) Fluorescence in situ hybridization with high-complexity repeat-free oligonucleotide probes generated by massively parallel synthesis. Chromosome Res 19:901–909

    CAS  PubMed Central  PubMed  Google Scholar 

  • Brickner JH, Walter P (2004) Gene recruitment of the activated INO1 locus to the nuclear membrane. PLoS Biol 2:e342

    PubMed Central  PubMed  Google Scholar 

  • Brown CR, Kennedy CJ, Delmar VA, Forbes DJ, Silver PA (2008a) Global histone acetylation induces functional genomic reorganization at mammalian nuclear pore complexes. Genes Dev 22:627–639

    CAS  PubMed Central  PubMed  Google Scholar 

  • Brown JM, Green J, Neves das RP, Wallace HAC, Smith AJH, Hughes J, Gray N, Taylor S, Wood WG, Higgs DR et al (2008b) Association between active genes occurs at nuclear speckles and is modulated by chromatin environment. J Cell Biol 182:1083–1097

    CAS  PubMed Central  PubMed  Google Scholar 

  • Buchwalter AL, Liang Y, Hetzer MW (2014) Nup50 is required for cell differentiation and exhibits transcription-dependent dynamics. Mol Biol Cell 25:2472–2484

    CAS  PubMed Central  PubMed  Google Scholar 

  • Capelson M, Liang Y, Schulte R, Mair W, Wagner U, Hetzer MW (2010) Chromatin-bound nuclear pore components regulate gene expression in higher eukaryotes. Cell 140:372–383

    CAS  PubMed Central  PubMed  Google Scholar 

  • Carlton PM (2008) Three-dimensional structured illumination microscopy and its application to chromosome structure. Chromosome Res 16:351–365

    CAS  PubMed  Google Scholar 

  • Casolari JM, Brown CR, Komili S, West J, Hieronymus H, Silver PA (2004) Genome-wide localization of the nuclear transport machinery couples transcriptional status and nuclear organization. Cell 117:427–439

    CAS  PubMed  Google Scholar 

  • Cremer M, von Hase J, Volm T, Brero A, Kreth G, Walter J, Fischer C, Solovei I, Cremer C, Cremer T (2001) Non-random radial higher-order chromatin arrangements in nuclei of diploid human cells. Chromosome Res 9:541–567

    CAS  PubMed  Google Scholar 

  • Cronshaw JM, Krutchinsky AN, Zhang W, Chait BT, Matunis MJ (2002) Proteomic analysis of the mammalian nuclear pore complex. J Cell Biol 158:915–927

    CAS  PubMed Central  PubMed  Google Scholar 

  • D’Angelo MA, Hetzer MW (2008) Structure, dynamics and function of nuclear pore complexes. Trends Cell Biol 18:456–466

    PubMed Central  PubMed  Google Scholar 

  • D’Angelo MA, Gomez-Cavazos JS, Mei A, Lackner DH, Hetzer MW (2012) A change in nuclear pore complex composition regulates cell differentiation. Dev Cell 22:446–458

    PubMed Central  PubMed  Google Scholar 

  • Demmerle J, Koch AJ, Holaska JM (2012) The nuclear envelope protein emerin binds directly to histone deacetylase 3 (HDAC3) and activates HDAC3 activity. J Biol Chem 287:22080–22088

    CAS  PubMed Central  PubMed  Google Scholar 

  • Desprat R, Thierry-Mieg D, Lailler N, Lajugie J, Schildkraut C, Thierry-Mieg J, Bouhassira EE (2009) Predictable dynamic program of timing of DNA replication in human cells. Genome Res 19:2288–2299

    CAS  PubMed Central  PubMed  Google Scholar 

  • Di Masi A, D’Apice MR, Ricordy R, Tanzarella C, Novelli G (2008) The R527H mutation in LMNA gene causes an increased sensitivity to ionizing radiation. Cell Cycle 7:2030–2037

    PubMed  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. Dev. 137:3067–3077

    CAS  Google Scholar 

  • Dimitrova DS, Gilbert DM (1999) The spatial position and replication timing of chromosomal domains are both established in early G1 phase. Mol Cell 4:983–993

    CAS  PubMed  Google Scholar 

  • Dou H, Huang C, Van Nguyen T, Lu L-S, Yeh ETH (2011) SUMOylation and de-SUMOylation in response to DNA damage. FEBS Lett 585:2891–2896

    CAS  PubMed  Google Scholar 

  • Finlan LE, Sproul D, Thomson I, Boyle S, Kerr E, Perry P, Ylstra B, Chubb JR, Bickmore WA (2008) Recruitment to the nuclear periphery can alter expression of genes in human cells. PLoS Genet 4:e1000039

    PubMed Central  PubMed  Google Scholar 

  • Franks TM, Hetzer MW (2013) The role of Nup98 in transcription regulation in healthy and diseased cells. Trends Cell Biol 23:112–117

    CAS  PubMed Central  PubMed  Google Scholar 

  • Furukawa K (1999) LAP2 binding protein 1 (L2BP1/BAF) is a candidate mediator of LAP2-chromatin interaction. J Cell Sci 112:2485–2492

    CAS  PubMed  Google Scholar 

  • Giorgetti L, Galupa R, Nora EP, Piolot T, Lam F, Dekker J, Tiana G, Heard E (2014) Predictive polymer modeling reveals coupled fluctuations in chromosome conformation and transcription. Cell 157:950–963

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gonzalez-Suarez I, Redwood AB, Perkins SM, Vermolen B, Lichtensztejin D, Grotsky DA, Morgado-Palacin L, Gapud EJ, Sleckman BP, Sullivan T et al (2009) Novel roles for A-type lamins in telomere biology and the DNA damage response pathway. EMBO J 28:2414–2427

    CAS  PubMed Central  PubMed  Google Scholar 

  • Griffis ER, Altan N, Lippincott-Schwartz J, Powers MA (2002) Nup98 is a mobile nucleoporin with transcription-dependent dynamics. Mol Biol Cell 13:1282–1297

    CAS  PubMed Central  PubMed  Google Scholar 

  • Guelen L, Pagie L, Brasset E, Meuleman W, Faza MB, Talhout W, Eussen BH, de Klein A, Wessels L, de Laat W et al (2008) Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions. Nature 453:948–951

    CAS  PubMed  Google Scholar 

  • Hakim O, Sung M-H, Voss TC, Splinter E, John S, Sabo PJ, Thurman RE, Stamatoyannopoulos JA, de Laat W, Hager GL (2011) Diverse gene reprogramming events occur in the same spatial clusters of distal regulatory elements. Genome Res 21:697–706

    CAS  PubMed Central  PubMed  Google Scholar 

  • Harr JC, Luperchio TR, Wong X, Cohen E, Wheelan SJ, Reddy KL (2015) Directed targeting of chromatin to the nuclear lamina is mediated by chromatin state and A-type lamins. J Cell Biol 208:33–52

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hatch EM, Fischer AH, Deerinck TJ, Hetzer MW (2013) Catastrophic nuclear envelope collapse in cancer cell micronuclei. Cell 154:47–60

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hiratani I, Ryba T, Itoh M, Yokochi T, Schwaiger M, Chang C-W, Lyou Y, Townes TM, Schübeler D, Gilbert DM (2008) Global reorganization of replication domains during embryonic stem cell differentiation. PLoS Biol 6:e245

    PubMed Central  PubMed  Google Scholar 

  • Hiratani I, Ryba T, Itoh M, Rathjen J, Kulik M, Papp B, Fussner E, Bazett-Jones DP, Plath K, Dalton S et al (2010) Genome-wide dynamics of replication timing revealed by in vitro models of mouse embryogenesis. Genome Res 20:155–169

    CAS  PubMed Central  PubMed  Google Scholar 

  • Horigome C, Oma Y, Konishi T, Schmid R, Marcomini I, Hauer MH, Dion V, Harata M, Gasser SM (2014) SWR1 and INO80 chromatin remodelers contribute to DNA double-strand break perinuclear anchorage site choice. Mol Cell 55:626–639

    CAS  PubMed  Google Scholar 

  • Jacinto FV, Benner C, Hetzer MW (2015) The nucleoporin Nup153 regulates embryonic stem cell pluripotency through gene silencing. Genes Dev 9:1224–1238

    Google Scholar 

  • Kalhor R, Tjong H, Jayathilaka N, Alber F, Chen L (2012) Genome architectures revealed by tethered chromosome conformation capture and population-based modeling. Nat Biotechnol 30:90–98

    CAS  Google Scholar 

  • Kalocsay M, Hiller NJ, Jentsch S (2009) Chromosome-wide Rad51 spreading and SUMO-H2A.Z-dependent chromosome fixation in response to a persistent DNA double-strand break. Mol Cell 33:335–343

    CAS  PubMed  Google Scholar 

  • Kalverda B, Fornerod M (2010) Characterization of genome-nucleoporin interactions in Drosophila links chromatin insulators to the nuclear pore complex. Cell Cycle 9:4812–4817

    CAS  PubMed  Google Scholar 

  • Kalverda B, Pickersgill H, Shloma VV, Fornerod M (2010) Nucleoporins directly stimulate expression of developmental and cell-cycle genes inside the nucleoplasm. Cell 140:360–371

    CAS  PubMed  Google Scholar 

  • Kasper LH, Brindle PK, Schnabel CA, Pritchard CE, Cleary ML, van Deursen JM (1999) CREB binding protein interacts with nucleoporin-specific FG repeats that activate transcription and mediate NUP98-HOXA9 oncogenicity. Mol Cell Biol 19:764–776

    CAS  PubMed Central  PubMed  Google Scholar 

  • Khadaroo B, Teixeira MT, Luciano P, Eckert-Boulet N, Germann SM, Simon MN, Gallina I, Abdallah P, Gilson E, Géli V et al (2009) The DNA damage response at eroded telomeres and tethering to the nuclear pore complex. Nat Cell Biol 11:980–987

    CAS  PubMed  Google Scholar 

  • Kind J, Pagie L, Ortabozkoyun H, Boyle S, de Vries SS, Janssen H, Amendola M, Nolen LD, Bickmore WA, van Steensel B (2013) Single-cell dynamics of genome-nuclear lamina interactions. Cell 153:178–192

    CAS  PubMed  Google Scholar 

  • Kubben N, Adriaens M, Meuleman W, Voncken JW, van Steensel B, Misteli T (2012) Mapping of lamin A- and progerin-interacting genome regions. Chromosoma 121:447–464

    CAS  PubMed Central  PubMed  Google Scholar 

  • Küpper K, Kölbl A, Biener D, Dittrich S, von Hase J, Thormeyer T, Fiegler H, Carter NP, Speicher MR, Cremer T et al (2007) Radial chromatin positioning is shaped by local gene density, not by gene expression. Chromosoma 116:285–306

    PubMed Central  PubMed  Google Scholar 

  • Lee DC, Welton KL, Smith ED, Kennedy BK (2009) A-type nuclear lamins act as transcriptional repressors when targeted to promoters. Exp Cell Res 315:996–1007

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lemaître C, Fischer B, Kalousi A, Hoffbeck A-S, Guirouilh-Barbat J, Shahar OD, Genet D, Goldberg M, Betrand P, Lopez B et al (2012) The nucleoporin 153, a novel factor in double-strand break repair and DNA damage response. Oncogene 31:4803–4809

    PubMed  Google Scholar 

  • Lemaître C, Grabarz A, Tsouroula K, Andronov L, Furst A, Pankotai T, Heyer V, Rogier M, Attwood KM, Kessler P et al (2014) Nuclear position dictates DNA repair pathway choice. Genes Dev 28:2450–2463

    PubMed Central  PubMed  Google Scholar 

  • Liang Y, Franks TM, Marchetto MC, Gage FH, Hetzer MW (2013) Dynamic association of NUP98 with the human genome. PLoS Genet 9:e1003308

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lieberman-Aiden E, van Berkum NL, Williams L, Imakaev M, Ragoczy T, Telling A, Amit I, Lajoie BR, Sabo PJ, Dorschner MO et al (2009) Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326:289–293

    CAS  PubMed Central  PubMed  Google Scholar 

  • Liu B, Wang J, Chan KM, Tjia WM, Deng W, Guan X, Huang J, Li KM, Chau PY, Chen DJ et al (2005) Genomic instability in laminopathy-based premature aging. Nat Med 11:780–785

    CAS  PubMed  Google Scholar 

  • Lund EG, Duband-Goulet I, Oldenburg A, Buendia B, Collas P (2015) Distinct features of lamin A-interacting chromatin domains mapped by ChIP-sequencing from sonicated or micrococcal nuclease-digested chromatin. Nucl. 6:30–39

    Google Scholar 

  • Ma J, Goryaynov A, Sarma A, Yang W (2012) Self-regulated viscous channel in the nuclear pore complex. Proc Natl Acad Sci U S A 109:7326–7331

    CAS  PubMed Central  PubMed  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

    CAS  PubMed Central  PubMed  Google Scholar 

  • Malhas A, Lee CF, Sanders R, Saunders NJ, Vaux DJ (2007) Defects in lamin B1 expression or processing affect interphase chromosome position and gene expression. J Cell Biol 176:593–603

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mansharamani M, Hewetson A, Chilton BS (2001) Cloning and characterization of an atypical Type IV P-type ATPase that binds to the RING motif of RUSH transcription factors. J Biol Chem 276:3641–3649

    CAS  PubMed  Google Scholar 

  • Margalit A, Brachner A, Gotzmann J, Foisner R, Gruenbaum Y (2007) Barrier-to-autointegration factor–a BAFfling little protein. Trends Cell Biol 17:202–208

    CAS  PubMed  Google Scholar 

  • Markaki Y, Smeets D, Fiedler S, Schmid VJ, Schermelleh L, Cremer T, Cremer M (2012) The potential of 3D-FISH and super-resolution structured illumination microscopy for studies of 3D nuclear architecture. BioEssays 34:412–426

    PubMed  Google Scholar 

  • Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y et al (2007) ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science 316:1160–1166

    CAS  PubMed  Google Scholar 

  • McCord RP, Nazario-Toole A, Zhang H, Chines PS, Zhan Y, Erdos MR, Collins FS, Dekker J, Cao K (2013) Correlated alterations in genome organization, histone methylation, and DNA-lamin A/C interactions in Hutchinson–Gilford progeria syndrome. Genome Res 23:260–269

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mendjan S, Taipale M, Kind J, Holz H, Gebhardt P, Schelder M, Vermeulen M, Buscaino A, Duncan K, Mueller J et al (2006) Nuclear pore components are involved in the transcriptional regulation of dosage compensation in Drosophila. Mol Cell 21:811–823

    CAS  PubMed  Google Scholar 

  • Meuleman W, Peric-Hupkes D, Kind J, Beaudry J-B, Pagie L, Kellis M, Reinders M, Wessels L, van Steensel B (2013) Constitutive nuclear lamina-genome interactions are highly conserved and associated with A/T-rich sequence. Genome Res 23:270–280

    CAS  PubMed Central  PubMed  Google Scholar 

  • Morey C, Kress C, Bickmore WA (2009) Lack of bystander activation shows that localization exterior to chromosome territories is not sufficient to up-regulate gene expression. Genome Res 19:1184–1194

    CAS  PubMed Central  PubMed  Google Scholar 

  • Moudry P, Lukas C, Macurek L, Neumann B, Heriche J-K, Pepperkok R, Ellenberg J, Hodny Z, Lukas J, Bartek J (2012) Nucleoporin NUP153 guards genome integrity by promoting nuclear import of 53BP1. Cell Death Differ 19:798–807

    CAS  PubMed Central  PubMed  Google Scholar 

  • Müller I, Boyle S, Singer RH, Bickmore WA, Chubb JR (2010) Stable morphology, but dynamic internal reorganisation, of interphase human chromosomes in living cells. PLoS One 5:e11560

    PubMed Central  PubMed  Google Scholar 

  • Nagai S, Dubrana K, Tsai-Pflugfelder M, Davidson MB, Roberts TM, Brown GW, Varela E, Hediger F, Gasser SM, Krogan NJ (2008) Functional targeting of DNA damage to a nuclear pore-associated SUMO-dependent ubiquitin ligase. Science 322:597–602

    CAS  PubMed Central  PubMed  Google Scholar 

  • Németh A, Conesa A, Santoyo-Lopez J, Medina I, Montaner D, Péterfia B, Solovei I, Cremer T, Dopazo J, Längst G (2010) Initial genomics of the human nucleolus. PLoS Genet 6:e1000889

    PubMed Central  PubMed  Google Scholar 

  • Nili E, Cojocaru GS, Kalma Y, Ginsberg D, Copeland NG, Gilbert DJ, Jenkins NA, Berger R, Shaklai S, Amariglio N et al (2001) Nuclear membrane protein LAP2beta mediates transcriptional repression alone and together with its binding partner GCL (germ-cell-less). J Cell Sci 114:3297–3307

    CAS  PubMed  Google Scholar 

  • O’Keefe RT, Henderson SC, Spector DL (1992) Dynamic organization of DNA replication in mammalian cell nuclei: spatially and temporally defined replication of chromosome-specific alpha-satellite DNA sequences. J Cell Biol 116:1095–1110

    PubMed  Google Scholar 

  • Okamoto A, Utani K, Shimizu N (2012) DNA replication occurs in all lamina positive micronuclei, but never in lamina negative micronuclei. Mutagenesis 27:323–327

    CAS  PubMed  Google Scholar 

  • Oza P, Peterson CL (2010) Opening the DNA repair toolbox: localization of DNA double strand breaks to the nuclear periphery. Cell Cycle 9:43–49

    CAS  PubMed  Google Scholar 

  • Palancade B, Doye V (2008) Sumoylating and desumoylating enzymes at nuclear pores: underpinning their unexpected duties? Trends Cell Biol 18:174–183

    CAS  PubMed  Google Scholar 

  • Palancade B, Liu X, Garcia-Rubio M, Aguilera A, Zhao X, Doye V (2007) Nucleoporins prevent DNA damage accumulation by modulating Ulp1-dependent sumoylation processes. Mol Biol Cell 18:2912–2923

    CAS  PubMed Central  PubMed  Google Scholar 

  • Passarge E (1979) Emil Heitz and the concept of heterochromatin: longitudinal chromosome differentiation was recognized 50 years ago. Am J Hum Genet 31:106–115

    CAS  PubMed Central  PubMed  Google Scholar 

  • Peric-Hupkes D, Meuleman W, Pagie L, Bruggeman SWM, Solovei I, Brugman W, Gräf S, Flicek P, Kerkhoven RM, van Lohuizen M et al (2010) Molecular maps of the reorganization of genome-nuclear lamina interactions during differentiation. Mol Cell 38:603–613

    CAS  PubMed  Google Scholar 

  • Pickersgill H, Kalverda B, de Wit E, Talhout W, Fornerod M, van Steensel B (2006) Characterization of the Drosophila melanogaster genome at the nuclear lamina. Nat Genet 38:1005–1014

    CAS  PubMed  Google Scholar 

  • Pinheiro I, Margueron R, Shukeir N, Eisold M, Fritzsch C, Richter FM, Mittler G, Genoud C, Goyama S, Kurokawa M et al (2012) Prdm3 and Prdm16 are H3K9me1 methyltransferases required for mammalian heterochromatin integrity. Cell 150:948–960

    CAS  PubMed  Google Scholar 

  • Rabut G, Doye V, Ellenberg J (2004) Mapping the dynamic organization of the nuclear pore complex inside single living cells. Nat Cell Biol 6:1114–1121

    CAS  PubMed  Google Scholar 

  • Raices M, D’Angelo MA (2012) Nuclear pore complex composition: a new regulator of tissue-specific and developmental functions. Nat Rev Mol Cell Biol 13:687–699

    CAS  PubMed  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

    CAS  PubMed  Google Scholar 

  • Redwood AB, Perkins SM, Vanderwaal RP, Feng Z, Biehl KJ, Gonzalez-Suarez I, Morgado-Palacin L, Shi W, Sage J, Roti-Roti JL et al (2011) A dual role for A-type lamins in DNA double-strand break repair. Cell Cycle 10:2549–2560

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ricci MA, Manzo C, García-Parajo MF, Lakadamyali M, Cosma MP (2015) Chromatin fibers are formed by heterogeneous groups of nucleosomes in vivo. Cell 160:1145–1158

    CAS  PubMed  Google Scholar 

  • Schermelleh L, Carlton PM, Haase S, Shao L, Winoto L, Kner P, Burke B, Cardoso MC, Agard DA, Gustafsson MGL et al (2008) Subdiffraction multicolor imaging of the nuclear periphery with 3D structured illumination microscopy. Science 320:1332–1336

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schoenfelder S, Sexton T, Chakalova L, Cope NF, Horton A, Andrews S, Kurukuti S, Mitchell JA, Umlauf D, Dimitrova DS et al (2010) Preferential associations between co-regulated genes reveal a transcriptional interactome in erythroid cells. Nat Genet 42:53–61

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sexton T, Yaffe E, Kenigsberg E, Bantignies F, Leblanc B, Hoichman M, Parrinello H, Tanay A, Cavalli G (2012) Three-dimensional folding and functional organization principles of the Drosophila genome. Cell 148:458–472

    CAS  PubMed  Google Scholar 

  • Shevelyov YY, Lavrov SA, Mikhaylova LM, Nurminsky ID, Kulathinal RJ, Egorova KS, Rozovsky YM, Nurminsky DI (2009) The B-type lamin is required for somatic repression of testis-specific gene clusters. Proc Natl Acad Sci U S A 106:3282–3287

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shimi T, Pfleghaar K, Kojima S, Pack C-G, Solovei I, Goldman AE, Adam SA, Shumaker DK, Kinjo M, Cremer T et al (2008) The A- and B-type nuclear lamin networks: microdomains involved in chromatin organization and transcription. Genes Dev 22:3409–3421

    CAS  PubMed Central  PubMed  Google Scholar 

  • Simonis M, Klous P, Splinter E, Moshkin Y, Willemsen R, de Wit E, van Steensel B, de Laat W (2006) Nuclear organization of active and inactive chromatin domains uncovered by chromosome conformation capture-on-chip (4C). Nat Genet 38:1348–1354

    CAS  PubMed  Google Scholar 

  • Solovei I, Wang AS, Thanisch K, Schmidt CS, Krebs S, Zwerger M, Cohen TV, Devys D, Foisner R, Peichl L et al (2013) LBR and lamin A/C sequentially tether peripheral heterochromatin and inversely regulate differentiation. Cell 152:584–598

    CAS  PubMed  Google Scholar 

  • Soutoglou E, Dorn JF, Sengupta K, Jasin M, Nussenzweig A, Ried T, Danuser G, Misteli T (2007) Positional stability of single double-strand breaks in mammalian cells. Nat Cell Biol 9:675–682

    CAS  PubMed Central  PubMed  Google Scholar 

  • Stack SM, Brown DB, Dewey WC (1977) Visualization of interphase chromosomes. J Cell Sci 26:281–299

    CAS  PubMed  Google Scholar 

  • Sutherland H, Bickmore WA (2009) Transcription factories: gene expression in unions? Nat Rev Genet 10:457–466

    CAS  PubMed  Google Scholar 

  • Taddei A, Van Houwe G, Hediger F, Kalck V, Cubizolles F, Schober H, Gasser SM (2006) Nuclear pore association confers optimal expression levels for an inducible yeast gene. Nature 441:774–778

    CAS  PubMed  Google Scholar 

  • Therizols P, Fairhead C, Cabal GG, Genovesio A, Olivo-Marin J-C, Dujon B, Fabre E (2006) Telomere tethering at the nuclear periphery is essential for efficient DNA double strand break repair in subtelomeric region. J Cell Biol 172:189–199

    CAS  PubMed Central  PubMed  Google Scholar 

  • Therizols P, Illingworth RS, Courilleau C, Boyle S, Wood AJ, Bickmore WA (2014) Chromatin decondensation is sufficient to alter nuclear organization in embryonic stem cells. Science 346:1238–1242

    CAS  PubMed  Google Scholar 

  • Thomson I, Gilchrist S, Bickmore WA, Chubb JR (2004) The radial positioning of chromatin is not inherited through mitosis but is established de novo in early G1. Curr Biol 14:166–172

    CAS  PubMed  Google Scholar 

  • Towbin BD, González-Aguilera C, Sack R, Gaidatzis D, Kalck V, Meister P, Askjaer P, Gasser SM (2012) Step-wise methylation of histone H3K9 positions heterochromatin at the nuclear periphery. Cell 150:934–947

    CAS  PubMed  Google Scholar 

  • Van Koningsbruggen S, Gierlinski M, Schofield P, Martin D, Barton GJ, Ariyurek Y, den Dunnen JT, Lamond AI (2010) High-resolution whole-genome sequencing reveals that specific chromatin domains from most human chromosomes associate with nucleoli. Mol Biol Cell 21:3735–3748

    PubMed Central  PubMed  Google Scholar 

  • Vaquerizas JM, Suyama R, Kind J, Miura K, Luscombe NM, Akhtar A (2010) Nuclear pore proteins nup153 and megator define transcriptionally active regions in the Drosophila genome. PLoS Genet 6:e1000846

    PubMed Central  PubMed  Google Scholar 

  • Varela I, Cadiñanos J, Pendás AM, Gutiérrez-Fernández A, Folgueras AR, Sánchez LM, Zhou Z, Rodríguez FJ, Stewart CL, Vega JA et al (2005) Accelerated ageing in mice deficient in Zmpste24 protease is linked to p53 signalling activation. Nature 437:564–568

    CAS  PubMed  Google Scholar 

  • Walter J, Schermelleh L, Cremer M, Tashiro S, Cremer T (2003) Chromosome order in HeLa cells changes during mitosis and early G1, but is stably maintained during subsequent interphase stages. J Cell Biol 160:685–697

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wang GG, Cai L, Pasillas MP, Kamps MP (2007) NUP98-NSD1 links H3K36 methylation to Hox-A gene activation and leukaemogenesis. Nat Cell Biol 9:804–812

    CAS  PubMed  Google Scholar 

  • Wen B, Wu H, Shinkai Y, Irizarry RA, Feinberg AP (2009) Large histone H3 lysine 9 dimethylated chromatin blocks distinguish differentiated from embryonic stem cells. Nat Genet 41:246–250

    CAS  PubMed Central  PubMed  Google Scholar 

  • Williams RRE, Azuara V, Perry P, Sauer S, Dvorkina M, Jørgensen H, Roix J, McQueen P, Misteli T, Merkenschlager M et al (2006) Neural induction promotes large-scale chromatin reorganisation of the Mash1 locus. J Cell Sci 119:132–140

    CAS  PubMed  Google Scholar 

  • Williamson I, Berlivet S, Eskeland R, Boyle S, Illingworth RS, Paquette D, Dostie J, Bickmore WA (2014) Spatial genome organization: contrasting views from chromosome conformation capture and fluorescence in situ hybridization. Genes Dev 28:2778–2791

    PubMed Central  PubMed  Google Scholar 

  • Woodfine K, Fiegler H, Beare DM, Collins JE, McCann OT, Young BD, Debernardi S, Mott R, Dunham I, Carter NP (2004) Replication timing of the human genome. Hum Mol Genet 13:191–202

    CAS  PubMed  Google Scholar 

  • Yaffe E, Tanay A (2011) Probabilistic modeling of Hi-C contact maps eliminates systematic biases to characterize global chromosomal architecture. Nat Genet 43:1059–1065

    CAS  PubMed  Google Scholar 

  • Ye Q, Callebaut I, Pezhman A, Courvalin JC, Worman HJ (1997) Domain-specific interactions of human HP1-type chromodomain proteins and inner nuclear membrane protein LBR. J Biol Chem 272:14983–14989

    CAS  PubMed  Google Scholar 

  • Yokochi T, Gilbert DM (2007) Replication labeling with halogenated thymidine analogs. Curr Protoc Cell Biol. Chapter 22: Unit 22.10

  • Zhang H, Saitoh H, Matunis MJ (2002) Enzymes of the SUMO modification pathway localize to filaments of the nuclear pore complex. Mol Cell Biol 22:6498–6508

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang Y, McCord RP, Ho Y-J, Lajoie BR, Hildebrand DG, Simon AC, Becker MS, Alt FW, Dekker J (2012) Spatial organization of the mouse genome and its role in recurrent chromosomal translocations. Cell 148:908–921

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang CZ, Spektor A, Cornils H, Francis JM, Jackson EK, Liu S, Meyerson M, Pellman D (2015) Chromothripsis from DNA damage in micronuclei. Nature 522:179–184

    CAS  PubMed  Google Scholar 

  • Zhao X, Wu C-Y, Blobel G (2004) Mlp-dependent anchorage and stabilization of a desumoylating enzyme is required to prevent clonal lethality. J Cell Biol 167:605–611

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zhou L, Panté N (2010) The nucleoporin Nup153 maintains nuclear envelope architecture and is required for cell migration in tumor cells. FEBS Lett 584:3013–3020

    CAS  PubMed  Google Scholar 

  • Zink D, Bornfleth H, Visser A, Cremer C, Cremer T (1999) Organization of early and late replicating DNA in human chromosome territories. Exp Cell Res 1247:176–188

    Google Scholar 

  • Zuleger N, Boyle S, Kelly DA, de Las Heras JI, Lazou V, Korfali N, Batrakou DG, Randles KN, Morris GE, Harrison DJ et al (2013) Specific nuclear envelope transmembrane proteins can promote the location of chromosomes to and from the nuclear periphery. Genome Biol 14:R14

    PubMed Central  PubMed  Google Scholar 

  • Zullo JM, Demarco IA, Piqué-Regi R, Gaffney DJ, Epstein CB, Spooner CJ, Luperchio TR, Bernstein BE, Pritchard JK, Reddy KL et al (2012) DNA sequence-dependent compartmentalization and silencing of chromatin at the nuclear lamina. Cell 149:1474–1487

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Shelagh Boyle for the use of the micrograph in Fig. 2.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Wendy A. Bickmore.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Funding information

Wendy A. Bickmore is supported by the Medical Research Council UK and by European Research Council Advanced Grant 249956.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lemaître, C., Bickmore, W.A. Chromatin at the nuclear periphery and the regulation of genome functions. Histochem Cell Biol 144, 111–122 (2015). https://doi.org/10.1007/s00418-015-1346-y

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00418-015-1346-y

Keywords

Navigation