Skip to main content
SpringerLink
Log in

Local and Global Epigenetic Regulation of V(D)J Recombination

  • Chapter
  • First Online:
Epigenetic Regulation of Lymphocyte Development

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 356))

Abstract

Despite using the same Rag recombinase machinery expressed in both lymphocyte lineages, V(D)J recombination of immunoglobulins only occurs in B cells and T cell receptor recombination is confined to T cells. This vital segregation of recombination targets is governed by the coordinated efforts of several epigenetic mechanisms that control both the general chromatin accessibility of these loci to the Rag recombinase, and the movement and synapsis of distal gene segments in these enormous multigene AgR loci, in a lineage and developmental stage-specific manner. These mechanisms operate both locally at individual gene segments and AgR domains, and globally over large distances in the nucleus. Here we will discuss the roles of several epigenetic components that regulate V(D)J recombination of the immunoglobulin heavy chain locus in B cells, both in the context of the locus itself, and of its 3D nuclear organization, focusing in particular on non-coding RNA transcription. We will also speculate about how several newly described epigenetic mechanisms might impact on AgR regulation.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abarrategui I, Krangel MS (2006) Regulation of T cell receptor-alpha gene recombination by transcription. Nat Immunol 7:1109–1115

    Article  PubMed  CAS  Google Scholar 

  • Abarrategui I, Krangel MS (2007) Noncoding transcription controls downstream promoters to regulate T cell receptor alpha recombination. EMBO J 26:4380–4390

    Article  PubMed  CAS  Google Scholar 

  • Abarrategui I, Krangel MS (2009) Germline transcription: a key regulator of accessibility and recombination. Adv Exp Med Biol 650:93–102

    Article  PubMed  CAS  Google Scholar 

  • Afshar R, Pierce S, Bolland DJ, Corcoran A, Oltz EM (2006) Regulation of IgH gene assembly: role of the intronic enhancer and 5′DQ52 region in targeting DHJH recombination. J Immunol 176:2439–2447

    PubMed  CAS  Google Scholar 

  • Bacher CP, Guggiari M, Brors B, Augui S, Clerc P, Avner P, Eils R, Heard E (2006) Transient colocalization of X-inactivation centres accompanies the initiation of X-inactivation. Nat Cell Biol 8:293–299

    Article  PubMed  CAS  Google Scholar 

  • Bates JG, Cado D, Nolla H, Schlissel MS (2007) Chromosomal position of a VH gene segment determines its activation and inactivation as a substrate for V(D)J recombination. J Exp Med 204:3247–3256

    Article  PubMed  CAS  Google Scholar 

  • Bernstein BE, Kamal M, Lindblad-Toh K, Bekiranov S, Bailey DK, Huebert DJ, McMahon S, Karlsson EK, Kulbokas EJ III, Gingeras TR, Schreiber SL, Lander ES (2005) Genomic maps and comparative analysis of histone modifications in human and mouse. Cell 120:169–181

    Article  PubMed  CAS  Google Scholar 

  • Bertolino E, Reddy K, Medina KL, Parganas E, Ihle J, Singh H (2005) Regulation of interleukin 7-dependent immunoglobulin heavy-chain variable gene rearrangements by transcription factor STAT5. Nat Immunol 6:836–843

    Article  PubMed  CAS  Google Scholar 

  • Bolland DJ, Wood AL, Afshar R, Featherstone K, Oltz EM, Corcoran AE (2007) Antisense intergenic transcription precedes Igh D-to-J recombination and is controlled by the intronic enhancer Emu. Mol Cell Biol 27:5523–5533

    Article  PubMed  CAS  Google Scholar 

  • Bolland DJ, Wood AL, Johnston CM, Bunting SF, Morgan G, Chakalova L, Fraser PJ, Corcoran AE (2004) Antisense intergenic transcription in V(D)J recombination. Nat Immunol 5:630–637

    Article  PubMed  CAS  Google Scholar 

  • Carninci P, Kasukawa T, Katayama S, Gough J, Frith MC, Maeda N, Oyama R, Ravasi T, Lenhard B, Wells C, Kodzius R, Shimokawa K, Bajic VB, Brenner SE, Batalov S, Forrest AR, Zavolan M, Davis MJ, Wilming LG, Aidinis V, Allen JE, Ambesi-Impiombato A, Apweiler R, Aturaliya RN, Bailey TL, Bansal M, Baxter L, Beisel KW, Bersano T, Bono H, Chalk AM, Chiu KP, Choudhary V, Christoffels A, Clutterbuck DR, Crowe ML, Dalla E, Dalrymple BP, de Bono B, Della Gatta G, di Bernardo D, Down T, Engstrom P, Fagiolini M, Faulkner G, Fletcher CF, Fukushima T, Furuno M, Futaki S, Gariboldi M, Georgii-Hemming P, Gingeras TR, Gojobori T, Green RE, Gustincich S, Harbers M, Hayashi Y, Hensch TK, Hirokawa N, Hill D, Huminiecki L, Iacono M, Ikeo K, Iwama A, Ishikawa T, Jakt M, Kanapin A, Katoh M, Kawasawa Y, Kelso J, Kitamura H, Kitano H, Kollias G, Krishnan SP, Kruger A, Kummerfeld SK, Kurochkin IV, Lareau LF, Lazarevic D, Lipovich L, Liu J, Liuni S, McWilliam S, Madan Babu M, Madera M, Marchionni L, Matsuda H, Matsuzawa S, Miki H, Mignone F, Miyake S, Morris K, Mottagui-Tabar S, Mulder N, Nakano N, Nakauchi H, Ng P, Nilsson R, Nishiguchi S, Nishikawa S et al (2005) The transcriptional landscape of the mammalian genome. Science 309:1559–1563

    Article  PubMed  CAS  Google Scholar 

  • Chakraborty T, Chowdhury D, Keyes A, Jani A, Subrahmanyam R, Ivanova I, Sen R (2007) Repeat organization and epigenetic regulation of the DH-Cmu domain of the immunoglobulin heavy-chain gene locus. Mol Cell 27:842–850

    Article  PubMed  CAS  Google Scholar 

  • Chakraborty T, Perlot T, Subrahmanyam R, Jani A, Goff PH, Zhang Y, Ivanova I, Alt FW, Sen R (2009) A 220-nucleotide deletion of the intronic enhancer reveals an epigenetic hierarchy in immunoglobulin heavy chain locus activation. J Exp Med 206:1019–1027

    Article  PubMed  CAS  Google Scholar 

  • Chowdhury D, Sen R (2001) Stepwise activation of the immunoglobulin mu heavy chain gene locus. Embo J 20:6394–6403

    Article  PubMed  CAS  Google Scholar 

  • Chowdhury D, Sen R (2003) Transient IL-7/IL-7R signaling provides a mechanism for feedback inhibition of immunoglobulin heavy chain gene rearrangements. Immunity 18:229–241

    Article  PubMed  CAS  Google Scholar 

  • Clemson CM, Hutchinson JN, Sara SA, Ensminger AW, Fox AH, Chess A, Lawrence JB (2009) An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles. Mol Cell 33:717–726

    Article  PubMed  CAS  Google Scholar 

  • Corcoran AE (2005) Immunoglobulin locus silencing and allelic exclusion. Semin Immunol 17:141–154

    Article  PubMed  CAS  Google Scholar 

  • Corcoran AE, Riddell A, Krooshoop D, Venkitaraman AR (1998) Impaired immunoglobulin gene rearrangement in mice lacking the IL-7 receptor. Nature 391:904–907

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Degner SC, Wong TP, Jankevicius G, Feeney AJ (2009) Cutting edge: developmental stage-specific recruitment of cohesin to CTCF sites throughout immunoglobulin loci during B lymphocyte development. J Immunol 182:44–48

    PubMed  CAS  Google Scholar 

  • Ebert A, McManus S, Tagoh H, Medvedovic J, Salvagiotto G, Novatchkova M, Tamir I, Sommer A, Jaritz M, Busslinger M (2011) The distal Vh gene cluster of the Igh locus contains disticnt regulatory elements with Pax5 transcription factor-dependent activity in pro-B cells. Immunity 34:175–187

    Article  PubMed  CAS  Google Scholar 

  • Engler P, Storb U (1999) Hypomethylation is necessary but not sufficient for V(D)J recombination within a transgenic substrate. Mol Immunol 36:1169–1173

    Article  PubMed  CAS  Google Scholar 

  • Featherstone K, Wood AL, Bowen AJ, Corcoran AE (2010) The mouse immunoglobulin heavy chain V–D intergenic sequence contains insulators that may regulate ordered V(D)J recombination. J Biol Chem 285:9327–9338

    Article  PubMed  CAS  Google Scholar 

  • Fraser P (2006) Transcriptional control thrown for a loop. Curr Opin Genet Dev 16:490–495

    Article  PubMed  CAS  Google Scholar 

  • Fuxa M, Skok J, Souabni A, Salvagiotto G, Roldan E, Busslinger M (2004) Pax5 induces V-to-DJ rearrangements and locus contraction of the immunoglobulin heavy-chain gene. Genes Dev 18:411–422

    Article  PubMed  CAS  Google Scholar 

  • Garrett FE, Emelyanov AV, Sepulveda MA, Flanagan P, Volpi S, Li F, Loukinov D, Eckhardt LA, Lobanenkov VV, Birshtein BK (2005) Chromatin architecture near a potential 3′ end of the igh locus involves modular regulation of histone modifications during B cell development and in vivo occupancy at CTCF sites. Mol Cell Biol 25:1511–1525

    Article  PubMed  CAS  Google Scholar 

  • Giallourakis CC, Franklin A, Guo C, Cheng HL, Yoon HS, Gallagher M, Perlot T, Andzelm M, Murphy AJ, Macdonald LE, Yancopoulos GD, Alt FW (2010) Elements between the IgH variable (V) and diversity (D) clusters influence antisense transcription and lineage-specific V(D)J recombination. Proc Natl Acad Sci USA 107:22207–22212

    Article  PubMed  CAS  Google Scholar 

  • Goebel P, Montalbano A, Ayers N, Kompfner E, Dickinson L, Webb CF, Feeney AJ (2002) High frequency of matrix attachment regions and cut-like protein x/CCAAT-displacement protein and B cell regulator of IgH transcription binding sites flanking Ig V region genes. J Immunol 169:2477–2487

    PubMed  CAS  Google Scholar 

  • Grazini U, Zanardi F, Citterio E, Casola S, Goding CR, Mcblane F (2010) The RING domain of RAG1 ubiquitylates histone H3: a novel activity in chromatin-mediated regulation of V(D)J joining. Mol Cell 37:282–293

    Article  PubMed  CAS  Google Scholar 

  • Gribnau J, Diderich K, Pruzina S, Calzolari R, Fraser P (2000) Intergenic transcription and developmental remodeling of chromatin subdomains in the human beta-globin locus. Mol Cell 5:377–386

    Article  PubMed  CAS  Google Scholar 

  • Guttman M, Amit I, Garber M, French C, Lin M, Feldser D, Huarte M, Zuk O, Carey B, Cassady J, Cabili M, Jaenisch R, Mikkelsen T, Jacks T, Hacohen N, Bernstein B, Kellis M, Regev A, Rinn J, Lander E (2009) Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458:223–227

    Article  PubMed  CAS  Google Scholar 

  • He Y, Vogelstein B, Velculescu VE, Papadopoulos N, Kinzler KW (2008) The antisense transcriptomes of human cells. Science 322:1855–1857

    Article  PubMed  CAS  Google Scholar 

  • Hewitt SL, Yin B, Ji Y, Chaumeil J, Marszalek K, Tenthorey J, Salvagiotto G, Steinel N, Ramsey LB, Ghysdael J, Farrar MA, Sleckman BP, Schatz DG, Busslinger M, Bassing CH, Skok JA (2009) RAG-1 and ATM coordinate monoallelic recombination and nuclear positioning of immunoglobulin loci. Nat Immunol 10:655–664

    Article  PubMed  CAS  Google Scholar 

  • Ho Y, Elefant F, Liebhaber SA, Cooke NE (2006) Locus control region transcription plays an active role in long-range gene activation. Mol Cell 23:365–375

    Article  PubMed  CAS  Google Scholar 

  • Holliday R (1990) Mechanisms for the control of gene activity during development. Biol Rev Camb Philos Soc 65:431–471

    Article  PubMed  CAS  Google Scholar 

  • Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D, Khalil AM, Zuk O, Amit I, Rabani M, Attardi LD, Regev A, Lander ES, Jacks T, Rinn JL (2010) A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell 142:409–419

    Article  PubMed  CAS  Google Scholar 

  • Jenuwein T, Forrester WC, Fernandez-Herrero LA, Laible G, Dull M, Grosschedl R (1997) Extension of chromatin accessibility by nuclear matrix attachment regions. Nature 385:269–272

    Article  PubMed  CAS  Google Scholar 

  • Jhunjhunwala S, van Zelm MC, Peak MM, Cutchin S, Riblet R, van Dongen JJ, Grosveld FG, Knoch TA, Murre C (2008) The 3D structure of the immunoglobulin heavy-chain locus: implications for long-range genomic interactions. Cell 133:265–279

    Article  PubMed  CAS  Google Scholar 

  • Jhunjhunwala S, van Zelm MC, Peak MM, Murre C (2009) Chromatin architecture and the generation of antigen receptor diversity. Cell 138:435–448

    Article  PubMed  CAS  Google Scholar 

  • Ji Y, Little AJ, Banerjee JK, Hao B, Oltz EM, Krangel MS, Schatz DG (2010a) Promoters, enhancers, and transcription target RAG1 binding during V(D)J recombination. J Exp Med 207:2809–2816

    Article  PubMed  CAS  Google Scholar 

  • Ji Y, Resch W, Corbett E, Yamane A, Casellas R, Schatz DG (2010b) The in vivo pattern of binding of RAG1 and RAG2 to antigen receptor loci. Cell 141:419–431

    Article  PubMed  CAS  Google Scholar 

  • Johnson K, Angelin-Duclos C, Park S, Calame KL (2003) Changes in histone acetylation are associated with differences in accessibility of V(H) gene segments to V–DJ recombination during B cell ontogeny and development. Mol Cell Biol 23:2438–2450

    Article  PubMed  CAS  Google Scholar 

  • Johnson K, Pflugh DL, Yu D, Hesslein DG, Lin KI, Bothwell AL, Thomas-Tikhonenko A, Schatz DG, Calame K (2004) B cell-specific loss of histone 3 lysine 9 methylation in the V(H) locus depends on Pax5. Nat Immunol 5:853–861

    Article  PubMed  CAS  Google Scholar 

  • Johnston CM, Wood AL, Bolland DJ, Corcoran AE (2006) Complete sequence assembly and characterization of the C57BL/6 mouse Ig heavy chain V region. J Immunol 176:4221–4234

    PubMed  CAS  Google Scholar 

  • Jones JM, Gellert M (2002) Ordered assembly of the V(D)J synaptic complex ensures accurate recombination. EMBO J 21:4162–4171

    Article  PubMed  CAS  Google Scholar 

  • Kapranov P, Cheng J, Dike S, Nix DA, Duttagupta R, Willingham AT, Stadler PF, Hertel J, Hackermuller J, Hofacker IL, Bell I, Cheung E, Drenkow J, Dumais E, Patel S, Helt G, Ganesh M, Ghosh S, Piccolboni A, Sementchenko V, Tammana H, Gingeras TR (2007) RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science 316:1484–1488

    Article  PubMed  CAS  Google Scholar 

  • Katayama S, Tomaru Y, Kasukawa T, Waki K, Nakanishi M, Nakamura M, Nishida H, Yap CC, Suzuki M, Kawai J, Suzuki H, Carninci P, Hayashizaki Y, Wells C, Frith M, Ravasi T, Pang KC, Hallinan J, Mattick J, Hume DA, Lipovich L, Batalov S, Engstrom PG, Mizuno Y, Faghihi MA, Sandelin A, Chalk AM, Mottagui-Tabar S, Liang Z, Lenhard B, Wahlestedt C (2005) Antisense transcription in the mammalian transcriptome. Science 309:1564–1566

    Article  PubMed  Google Scholar 

  • Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D, Thomas K, Presser A, Bernstein BE, van Oudenaarden A, Regev A, Lander ES, Rinn JL (2009) Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci USA 106:11667–11672

    Article  PubMed  CAS  Google Scholar 

  • Kim TK, Hemberg M, Gray JM, Costa AM, Bear DM, Wu J, Harmin DA, Laptewicz M, Barbara-Haley K, Kuersten S, Markenscoff-Papadimitriou E, Kuhl D, Bito H, Worley PF, Kreiman G, Greenberg ME (2010) Widespread transcription at neuronal activity-regulated enhancers. Nature 465:182–187

    Article  PubMed  CAS  Google Scholar 

  • Kosak ST, Skok JA, Medina KL, Riblet R, Le Beau MM, Fisher AG, Singh H (2002) Subnuclear compartmentalization of immunoglobulin loci during lymphocyte development. Science 296:158–162

    Article  PubMed  CAS  Google Scholar 

  • Koziol MJ, Rinn JL (2010) RNA traffic control of chromatin complexes. Curr Opin Genet Dev 20:142–148

    Article  PubMed  CAS  Google Scholar 

  • Lennon GG, Perry RP (1985) C mu-containing transcripts initiate heterogeneously within the IgH enhancer region and contain a novel 5′-nontranslatable exon. Nature 318:475–478

    Article  PubMed  CAS  Google Scholar 

  • Lieberman-Aiden E, van Berkum NL, Williams L, Imakaev M, Ragoczy T, Telling A, Amit I, Lajoie BR, Sabo PJ, Dorschner MO, Sandstrom R, Bernstein B, Bender MA, Groudine M, Gnirke A, Stamatoyannopoulos J, Mirny LA, Lander ES, Dekker J (2009) Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326:289–293

    Article  PubMed  CAS  Google Scholar 

  • Liu H, Schmidt-Supprian M, Shi Y, Hobeika E, Barteneva N, Jumaa H, Pelanda R, Reth M, Skok J, Rajewsky K (2007) Yin Yang 1 is a critical regulator of B cell development. Genes Dev 21:1179–1189

    Article  PubMed  CAS  Google Scholar 

  • Lucas JS, Bossen C, Murre C (2011) Transcription and recombination factories: common features? Curr Opin Cell Biol 23:318–324

    Article  PubMed  CAS  Google Scholar 

  • Maes J, Chappaz S, Cavelier P, O’Neill L, Turner B, Rougeon F, Goodhardt M (2006) Activation of V(D)J recombination at the IgH chain JH locus occurs within a 6-kilobase chromatin domain and is associated with nucleosomal remodeling. J Immunol 176:5409–5417

    PubMed  CAS  Google Scholar 

  • Maes J, O’Neill LP, Cavelier P, Turner BM, Rougeon F, Goodhardt M (2001) Chromatin remodeling at the Ig loci prior to V(D)J recombination. J Immunol 167:866–874

    PubMed  CAS  Google Scholar 

  • Malin S, Mcmanus S, Cobaleda C, Novatchkova M, Delogu A, Bouillet P, Strasser A, Busslinger M (2010) Role of STAT5 in controlling cell survival and immunoglobulin gene recombination during pro-B cell development. Nat Immunol 11:171–179

    Article  PubMed  CAS  Google Scholar 

  • Mao YS, Sunwoo H, Zhang B, Spector DL (2011) Direct visualization of the co-transcriptional assembly of a nuclear body by noncoding RNAs. Nat Cell Biol 13:95–101

    Article  PubMed  CAS  Google Scholar 

  • Masternak K, Peyraud N, Krawczyk M, Barras E, Reith W (2003) Chromatin remodeling and extragenic transcription at the MHC class II locus control region. Nat Immunol 4:132–137

    Article  PubMed  CAS  Google Scholar 

  • Matthews AG, Kuo AJ, Ramon-Maiques S, Han S, Champagne KS, Ivanov D, Gallardo M, Carney D, Cheung P, Ciccone DN, Walter KL, Utz PJ, Shi Y, Kutateladze TG, Yang W, Gozani O, Oettinger MA (2007) RAG2 PHD finger couples histone H3 lysine 4 trimethylation with V(D)J recombination. Nature 450:1106–1110

    Article  PubMed  CAS  Google Scholar 

  • Mercer TR, Dinger ME, Mattick JS (2009) Long non-coding RNAs: insights into functions. Nat Rev Genet 10:155–159

    Article  PubMed  CAS  Google Scholar 

  • Mitchell JA, Fraser P (2008) Transcription factories are nuclear subcompartments that remain in the absence of transcription. Genes Dev 22:20–25

    Article  PubMed  CAS  Google Scholar 

  • Mito Y, Henikoff JG, Henikoff S (2005) Genome-scale profiling of histone H3.3 replacement patterns. Nat Genet 37:1090–1097

    Article  PubMed  CAS  Google Scholar 

  • Morshead KB, Ciccone DN, Taverna SD, Allis CD, Oettinger MA (2003) Antigen receptor loci poised for V(D)J rearrangement are broadly associated with BRG1 and flanked by peaks of histone H3 dimethylated at lysine 4. Proc Natl Acad Sci USA 100:11577–11582

    Article  PubMed  CAS  Google Scholar 

  • Mostoslavsky R, Singh N, Kirillov A, Pelanda R, Cedar H, Chess A, Bergman Y (1998) Kappa chain monoallelic demethylation and the establishment of allelic exclusion. Genes Dev 12:1801–1811

    Article  PubMed  CAS  Google Scholar 

  • Nagano T, Mitchell JA, Sanz LA, Pauler FM, Ferguson-Smith AC, Feil R, Fraser P (2008) The Air noncoding RNA epigenetically silences transcription by targeting G9a to chromatin. Science 322:1717–1720

    Article  PubMed  CAS  Google Scholar 

  • Ng HH, Robert F, Young RA, Struhl K (2003) Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity. Mol Cell 11:709–719

    Article  PubMed  CAS  Google Scholar 

  • Nitschke L, Kestler J, Tallone T, Pelkonen S, Pelkonen J (2001) Deletion of the DQ52 element within the Ig heavy chain locus leads to a selective reduction in VDJ recombination and altered D gene usage. J Immunol 166:2540–2552

    PubMed  CAS  Google Scholar 

  • Orom UA, Derrien T, Beringer M, Gumireddy K, Gardini A, Bussotti G, Lai F, Zytnicki M, Notredame C, Huang Q, Guigo R, Shiekhattar R (2010) Long noncoding RNAs with enhancer-like function in human cells. Cell 143:46–58

    Article  PubMed  CAS  Google Scholar 

  • Orphanides G, Reinberg D (2000) RNA polymerase II elongation through chromatin. Nature 407:471–475

    Article  PubMed  CAS  Google Scholar 

  • Osborne CS, Chakalova L, Brown KE, Carter D, Horton A, Debrand E, Goyenechea B, Mitchell JA, Lopes S, Reik W, Fraser P (2004) Active genes dynamically colocalize to shared sites of ongoing transcription. Nat Genet 36:1065–1071

    Article  PubMed  CAS  Google Scholar 

  • Osborne CS, Chakalova L, Mitchell JA, Horton A, Wood AL, Bolland DJ, Corcoran AE, Fraser P (2007) Myc dynamically and preferentially relocates to a transcription factory occupied by Igh. PLoS Biol 5:e192

    Article  PubMed  CAS  Google Scholar 

  • Osipovich OA, Subrahmanyam R, Pierce S, Sen R, Oltz EM (2009) Cutting edge: SWI/SNF mediates antisense Igh transcription and locus-wide accessibility in B cell precursors. J Immunol 183:1509–1513

    Article  PubMed  CAS  Google Scholar 

  • Pang KC, Dinger ME, Mercer TR, Malquori L, Grimmond SM, Chen W, Mattick JS (2009) Genome-wide identification of long noncoding RNAs in CD8 + T cells. J Immunol 182:7738–7748

    Article  PubMed  CAS  Google Scholar 

  • Papantonis A, Larkin JD, Wada Y, Ohta Y, Ihara S, Kodama T, Cook PR (2010) Active RNA polymerases: mobile or immobile molecular machines? PLoS Biol 8:e1000419

    Article  PubMed  CAS  Google Scholar 

  • Pawlitzky I, Angeles CV, Siegel AM, Stanton ML, Riblet R, Brodeur PH (2006) Identification of a candidate regulatory element within the 5′ flanking region of the mouse Igh locus defined by pro-B cell-specific hypersensitivity associated with binding of PU.1, Pax5, and E2A. J Immunol 176:6839–6851

    PubMed  CAS  Google Scholar 

  • Perlot T, Alt FW, Bassing CH, Suh H, Pinaud E (2005) Elucidation of IgH intronic enhancer functions via germ-line deletion. Proc Natl Acad Sci USA 102:14362–14367

    Article  PubMed  CAS  Google Scholar 

  • Perlot T, Pawlitzky I, Manis JP, Zarrin AA, Brodeur PH, Alt FW (2010) Analysis of mice lacking DNaseI hypersensitive sites at the 5′ end of the IgH locus. PLoS One 5:e13992

    Article  PubMed  CAS  Google Scholar 

  • Phillips JE, Corces VG (2009) CTCF: master weaver of the genome. Cell 137:1194–1211

    Article  PubMed  Google Scholar 

  • Ponting CP, Oliver PL, Reik W (2009) Evolution and functions of long noncoding RNAs. Cell 136:629–641

    Article  PubMed  CAS  Google Scholar 

  • Ragoczy T, Bender MA, Telling A, Byron R, Groudine M (2006) The locus control region is required for association of the murine beta-globin locus with engaged transcription factories during erythroid maturation. Genes Dev 20:1447–1457

    Article  PubMed  CAS  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

    Article  PubMed  CAS  Google Scholar 

  • Reth MG, Alt FW (1984) Novel immunoglobulin heavy chains are produced from DJH gene segment rearrangements in lymphoid cells. Nature 312:418–423

    Article  PubMed  CAS  Google Scholar 

  • Reynaud D, Demarco IA, Reddy KL, Schjerven H, Bertolino E, Chen Z, Smale ST, Winandy S, Singh H (2008) Regulation of B cell fate commitment and immunoglobulin heavy-chain gene rearrangements by Ikaros. Nat Immunol 9:927–936

    Article  PubMed  CAS  Google Scholar 

  • Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, Goodnough LH, Helms JA, Farnham PJ, Segal E, Chang HY (2007) Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNAs. Cell 129:1311–1323

    Article  PubMed  CAS  Google Scholar 

  • Roldan E, Fuxa M, Chong W, Martinez D, Novatchkova M, Busslinger M, Skok JA (2005) Locus ‘decontraction’ and centromeric recruitment contribute to allelic exclusion of the immunoglobulin heavy-chain gene. Nat Immunol 6:31–41

    Article  PubMed  CAS  Google Scholar 

  • Sasaki YT, Ideue T, Sano M, Mituyama T, Hirose T (2009) MENepsilon/beta noncoding RNAs are essential for structural integrity of nuclear paraspeckles. Proc Natl Acad Sci U S A 106:2525–2530

    Article  PubMed  CAS  Google Scholar 

  • Sayegh C, Jhunjhunwala S, Riblet R, Murre C (2005) Visualization of looping involving the immunoglobulin heavy-chain locus in developing B cells. Genes Dev 19:322–327

    Article  PubMed  CAS  Google Scholar 

  • Schmitt S, Prestel M, Paro R (2005) Intergenic transcription through a polycomb group response element counteracts silencing. Genes Dev 19:697–708

    Article  PubMed  CAS  Google Scholar 

  • Schoenfelder S, Clay I, Fraser P (2010a) The transcriptional interactome: gene expression in 3D. Curr Opin Genet Dev 20:127–133

    Article  PubMed  CAS  Google Scholar 

  • Schoenfelder S, Sexton T, Chakalova L, Cope NF, Horton A, Andrews S, Kurukuti S, Mitchell JA, Umlauf D, Dimitrova DS, Eskiw CH, Luo Y, Wei CL, Ruan Y, Bieker JJ, Fraser P (2010b) Preferential associations between co-regulated genes reveal a transcriptional interactome in erythroid cells. Nat Genet 42:53–61

    Article  PubMed  CAS  Google Scholar 

  • Sessa L, Breiling A, Lavorgna G, Silvestri L, Casari G, Orlando V (2007) Noncoding RNA synthesis and loss of Polycomb group repression accompanies the colinear activation of the human HOXA cluster. RNA 13:223–239

    Article  PubMed  CAS  Google Scholar 

  • Shevtsov SP, Dundr M (2011) Nucleation of nuclear bodies by RNA. Nat Cell Biol 13:167–173

    Article  PubMed  CAS  Google Scholar 

  • Sleutels F, Zwart R, Barlow DP (2002) The non-coding Air RNA is required for silencing autosomal imprinted genes. Nature 415:810–813

    Article  PubMed  CAS  Google Scholar 

  • Spector DL (2003) The dynamics of chromosome organization and gene regulation. Annu Rev Biochem 72:573–608

    Article  PubMed  CAS  Google Scholar 

  • Stanhope-Baker P, Hudson KM, Shaffer AL, Constantinescu A, Schlissel MS (1996) Cell type-specific chromatin structure determines the targeting of V(D)J recombinase activity in vitro. Cell 85:887–897

    Article  PubMed  CAS  Google Scholar 

  • Storb U, Arp B (1983) Methylation patterns of immunoglobulin genes in lymphoid cells: correlation of expression and differentiation with undermethylation. Proc Natl Acad Sci USA 80:6642–6646

    Article  PubMed  CAS  Google Scholar 

  • Su IH, Basavaraj A, Krutchinsky AN, Hobert O, Ullrich A, Chait BT, Tarakhovsky A (2003) Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement. Nat Immunol 4:124–131

    Article  PubMed  CAS  Google Scholar 

  • Sunwoo H, Dinger ME, Wilusz JE, Amaral PP, Mattick JS, Spector DL (2009) MEN epsilon/beta nuclear-retained non-coding RNAs are up-regulated upon muscle differentiation and are essential components of paraspeckles. Genome Res 19:347–359

    Article  PubMed  CAS  Google Scholar 

  • Thompson A, Timmers E, Schuurman RK, Hendriks RW (1995) Immunoglobulin heavy chain germ-line JH-C mu transcription in human precursor B lymphocytes initiates in a unique region upstream of DQ52. Eur J Immunol 25:257–261

    Article  PubMed  CAS  Google Scholar 

  • Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, Shi Y, Segal E, Chang HY (2010) Long noncoding RNA as modular scaffold of histone modification complexes. Science 329: 689–693

    Article  PubMed  CAS  Google Scholar 

  • Volpi EV, Chevret E, Jones T, Vatcheva R, Williamson J, Beck S, Campbell RD, Goldsworthy M, Powis SH, Ragoussis J, Trowsdale J, Sheer D (2000) Large-scale chromatin organization of the major histocompatibility complex and other regions of human chromosome 6 and its response to interferon in interphase nuclei. J Cell Sci 113(Pt 9):1565–1576

    PubMed  CAS  Google Scholar 

  • Wilson CJ, Chao DM, Imbalzano AN, Schnitzler GR, Kingston RE, Young RA (1996) RNA polymerase II holoenzyme contains SWI/SNF regulators involved in chromatin remodeling. Cell 84:235–244

    Article  PubMed  CAS  Google Scholar 

  • Xu C-R, Feeney AJ (2009) The epigenetic profile of Ig genes is dynamically regulated during B cell differentiation and is modulated by pre-B cell receptor signaling. J Immunol 182:1362–1369

    Article  PubMed  CAS  Google Scholar 

  • Xu CR, Schaffer L, Head SR, Feeney AJ (2008) Reciprocal patterns of methylation of H3K36 and H3K27 on proximal vs. distal IgVH genes are modulated by IL-7 and Pax5. Proc Natl Acad Sci USA 105:8685–8690

    Article  PubMed  CAS  Google Scholar 

  • Yancopoulos GD, Alt FW (1985) Developmentally controlled and tissue-specific expression of unrearranged VH gene segments. Cell 40:271–281

    Article  PubMed  CAS  Google Scholar 

  • Yang Q, Riblet R, Schildkraut CL (2005) Sites that direct nuclear compartmentalization are near the 5′ end of the mouse immunoglobulin heavy-chain locus. Mol Cell Biol 25:6021–6030

    Article  PubMed  CAS  Google Scholar 

  • Zhao J, Sun BK, Erwin JA, Song JJ, Lee JT (2008) Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science 322:750–756

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank all members of the Corcoran group and the Chromatin and Gene Expression Laboratory for helpful discussions. The Biotechnology and Biological Sciences Research Council, UK supported this work.

Author information

Authors and Affiliations

  1. Laboratory of Chromatin and Gene Expression, The Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK

    Louise S. Matheson & Anne E. Corcoran

Authors
  1. Louise S. Matheson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anne E. Corcoran
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anne E. Corcoran .

Editor information

Editors and Affiliations

  1. , Section of Molecular Biology, Division of Biology, Gilman Drive, 5113 Natural Sci. Bldg. 9500, La Jolla, 92093-0377, California, USA

    Cornelis Murre

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Matheson, L.S., Corcoran, A.E. (2011). Local and Global Epigenetic Regulation of V(D)J Recombination. In: Murre, C. (eds) Epigenetic Regulation of Lymphocyte Development. Current Topics in Microbiology and Immunology, vol 356. Springer, Berlin, Heidelberg. https://doi.org/10.1007/82_2011_137

Download citation

Publish with us

Policies and ethics

Search

Navigation