Epigenetics of antigen-receptor gene assembly

Current Opinion in Genetics and Development

Volumn 17, Issue 5, 2007, Pages 415-421

  Murre, Cornelis ^a  

^a UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

IMMUNOGLOBULIN; IMMUNOGLOBULIN LIGHT CHAIN; LYMPHOCYTE ANTIGEN RECEPTOR; STAT5 PROTEIN; T LYMPHOCYTE RECEPTOR; TRANSCRIPTION FACTOR E2A; TRANSCRIPTION FACTOR PAX5; TRANSCRIPTION FACTOR YY1;

ALLELIC EXCLUSION; B LYMPHOCYTE; CELL LINEAGE; CELL MATURATION; CHROMATIN STRUCTURE; DNA METHYLATION; EPIGENETICS; GENE LOCUS; GENE REARRANGEMENT; GENE SILENCING; GENETIC TRANSCRIPTION; HUMAN; NUCLEAR LOCALIZATION SIGNAL; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN EXPRESSION; REVIEW; SOMATIC HYPERMUTATION;

ANIMALS; EPIGENESIS, GENETIC; GENE EXPRESSION REGULATION; HUMANS; RECEPTORS, ANTIGEN;

EID: 35648946344     PISSN: 0959437X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.gde.2007.08.006     Document Type: Review

References (49)

1. Hesslein D.G., and Schatz D.G. Factors and forces controlling V(D)J recombination. Adv Immunol 78 (2001) 169-232
2. Mostoslavsky R., Alt F.W., and Bassing C.H. Chromatin dynamics and locus accessibility in the immune system. Nat Immunol 4 (2003) 603-606
3. Jung D., Gillourakis C., Mostoslavsky R., and Alt F.W. Mechanism and control of V(D)J recombination at the immunoglobulin heavy chain gene. Annu Rev Immunol 24 (2006) 541-570
4. Alt F.W., Yancopoulos G.D., Blackwell T.K., Wood C., Thomas E., Boss M., Coffman N., Rosenberg N., Tonegawa S., and Baltimore D. Ordered rearrangement of immunoglobulin heavy chain variable region segments. EMBO J 3 (1984) 1209-1219
5. Nussenzweig M.C., Shaw A.C., Sinn E., Danner D.B., Hohnes H.C., Morse III H.C., and Leder P. Allelic exclusion in transgenic mice that express the membrane form of Ig M. Science 236 (1988) 816-819
6. Manz J., Denis K., Witte O., Brinster R., and Storb U. Feedback inhibition of immunoglobulin gene rearrangement by membrane but not secreted μ heavy chains. J Exp Med 168 (1988) 1363-1381
7. von Boehmer H. Selection of the T-cell repertoire: receptor-controlled checkpoints in T-cell development. Adv Immunol 84 (2004) 201-238
8. Busslinger M. Transcriptional control of early B cell development. Annu Rev Immunol 22 (2004) 55-79
9. Ikawa T., Kawamoto H., Goldrath A.W., and Murre C. E proteins and Notch signaling cooperate to promote T cell lineage specification and commitment. J Exp Med 15 (2006) 1329-1342
10. Bertolino E., Reddy K., Medina K.L., Parganas E., Ihle J., and Singh H. Regulation of interleukin 7-dependent immunoglobulin heavy-chain variable gene rearrangements by transcription factor STAT5. Nat Immunol 6 (2005) 836-843
11. Roessler S., Györy I., Imhof S., Spivakov M., Williams R.R., Busslinger M., Fisher A.G., and Grosschedl R. Distinct promoters mediate the regulation of Ebf1 gene expression by IL-7 and Pax5. Mol Cell Biol 2 (2007) 2253-2258
12. Maier H., Ostraat R., Gao H., Fields S., Shinton S.A., Medina K., Ikawa T., Murre C., Singh H., Hardy R.R., and Hagman J. Early B cell factor cooperates with Runx1 and mediates epigenetic changes associated with mb-1 transcription. Nat Immunol 5 (2004) 1069-1077. In hematopoietic stem cells, the mb-1 promoter is hypermethylated. However, the promoter is progressively demethylated upon maturing into the pro-B cell compartment. Beyond the pro-B cell stage the mb-1 promoter is completely demethylated. Demethylation and chromatin remodeling at the mb-1 promoter is modulated by EBF. These observations suggest a regulatory network in which EBF acts upstream of Pax5 to promote B-lineage specification.
13. Rothenberg E.V. Regulatory factors for initial T lymphocyte lineage specification. Curr Opin Hematol 14 (2007) 322-329
14. Hoflinger S., Kesavan K., Fuxa M., Hutter C., Heavey B., Radtke F., and Busslinger M. Analysis of Notch1 function by in vitro T cell differentiation of Pax5 mutant lymphoid progenitors. J Immunol 15 (2004) 3935-3944. Evidence is presented demonstrating that Notch1-mediated signaling acts to induce the expression of GATA3 and TCF1. These data link Notch signaling, GATA3, and TCF1 in a common pathway to regulate T-lineage maturation.
15. Barndt R.J., Dai M., and Zhuang Y. Functions of E2A-HEB heterodimers in T-cell development revealed by a dominant negative mutation of HEB. Mol Cell Biol 20 (2000) 6677-6685
16. Murre C. Helix-loop-helix proteins and lymphocyte development. Nat Immunol 6 (2005) 1079-1086
17. Engel I., and Murre C. E2A proteins enforce a proliferation checkpoint in developing thymocytes. EMBO J 23 (2004) 202-211
18. Stanhope-Baker P., Hudson K.M., Shaffer A.L., Constantinescu A., and Schlissel M.S. Cell type-specific chromatin structure determines the targeting of V(D)J recombinase activity in vitro. Cell 14 (1996) 887-899. The V(D)J recombinase is expressed in both developing B-lineage and T-lineage cells. However, the rearrangement of antigen-receptor genes is tightly regulated. Using an in vitro approach, the investigators demonstrate that the lineage-specificity and stage-specificity of recombination is reflected in the chromatin accessibility.
19. Fuxa M., Skok J., Souabni A., Salvagiotto G., Roldan E., and Busslinger M. Pax5 induces V-DJ rearrangements and locus contraction of the immunoglobulin heavy-chain gene. Genes Dev 18 (2004) 411-422
20. H regions were severely perturbed. However, the expression patterns of Pax5, E2A, and EBF were not affected in the absence of YY1. These data raise the possibility that YY1 is involved in modulating Igh topology.
21. Romanow W.J., Langerak A.W., Goebel P., Wolvers-Tettero I.L., van Dongen J.J., Feeney S.J., and Murre C. E2A and EBF act in synergy with the V(D)J recombinase to generate a diverse immunoglobulin repertoire in nonlymphoid cells. Mol Cell 5 (2000) 343-353
22. Goebel P., Janney N., Valenzuela J.R., Romanow W.J., Murre C., and Feeney A.J. Localized gene-specific induction of accessibility to V(D)J recombination induced by E2A and early B cell factor in nonlymphoid cells. J Exp Med 194 (2001) 645-656
23. Inlay M.A., Tian H., Lin T., and Xu Y. Important roles for E protein binding sites within the immunoglobulin K chain intronic enhancer in activating VκJκ rearrangement. J Exp Med 203 (2006) 1721-1732
24. Quong M., Martensson A., Langerak A.W., Rivera R.R., Nemazee D., and Murre C. Receptor editing and marginal zone B cell development are regulated by the helix-loop-helix protein, E2A. J Exp Med 199 (2004) 1113-1120
25. Zhang Z., Espinoza C.R., Yu Z., Stephan R., He T., Williams G.S., Burrows P.D., Hagman J., Feeney A.J., and Cooper M.D. Transcription factor Pax5 (BSAP) transactivates the RAG-mediated V(H)-to-D(H)J(H) rearrangement of immunoglobulin genes. Nat Immunol 7 (2006) 616-624
26. H gene segments. Cell 40 (1985) 271-281
27. Kwon J., Imbalzano A.N., Mathews A., and Oettinger M.A. Accessibility of nucleosomal DNA to V(D)J cleavage is modulated by RSS positioning and HMG1. Mol Cell 2 (1998) 829-839
28. Golding A., Chandler S., Ballestar E., Wolffe A.P., and Schlissel M.S. Nucleosome structure completely inhibits in vitro cleavage by the V(D)J recombinase. EMBO J 18 (1999) 3712-3723
29. Chowdhury D., and Sen R. Stepwise activation of the immunoglobulin heavy chain gene locus. EMBO J 20 (2001) 6394-6403
30. Su I.H., Basavaraj A., Krutchinsky A.N., Hobert O., Ullrich A., Chait B.T., and Tarakhovsky A. Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement. Nat Immunol 4 (2003) 124-131. Ezh2 is a H3K27 methyltransferase that is associated with transcriptional repression. The investigators provide evidence that Ezh2 is required to promote, rather than inhibit, IgH V(D)J rearrangement that involves distal VH regions.
31. Johnson K., Pflugh D.L., Yu D., Hesslein D.G., Lin K.I., Bothwell A.L., Thomas-Tikhonenko A., Schatz D.G., and Calame K. B cell-specific loss of histone 3 lysine 9 methylation in the V(H) locus depends on Pax5. Nat Immunol 5 (2004) 853-861
32. Bergman Y., and Cedar H. A stepwise epigenetic process controls immunoglobulin allelic exclusion. Nat Rev Immunol 10 (2004) 753-761
33. Mostoslavsky R., Singh N., Kirillov A., Pelanda R., Cedar H., Chess A., and Bergman Y. Kappa chain monoallelic demethylation and the establishment of allelic exclusion. Genes Dev 15 (1998) 1801-1811. Evidence is provided for mono-allelic marking of the IgK loci. The IgK locus is CpG methylated in pro-B cells. Upon developmental progression the IgK alleles undergo progressive mono-allelic demethylation. It is proposed that methylation of CpG residues is important for the allelic exclusion mechanism.
34. Fraenkel S., Mostoslavsky R., Novobrantseva T.I., Pelanda R., Chaudhuri J., Esposito G., Jung S., Alt F.W., Rajewsky K., Cedar H., and Bergman Y. Allelic 'choice' governs somatic hypermutation in vivo at the immunoglobulin kappa-chain locus. Nat Immunol 8 (2007) 715-722
35. Bolland D.J., Wood A.L., Johnston C.M., Bunting S.F., Morgan G., Chakalova L., Fraser P.J., and Corcoran A.E. Antisense intergenic transcription in V(D)J recombination. Nat Immunol 5 (2004) 630-637
36. Abarrategui I., and Krangel M.S. Regulation of T cell receptor-alpha gene recombination by transcription. Nat Immunol 7 (2006) 1109-1115. Previous observations have indicated that germ-line transcription is associated with antigen-receptor gene rearrangements. Here, unambiguous evidence is provided that transcriptional elongation is required to promote TCRα VJ gene rearrangement.
37. Kosak S.T., Skok J.A., Medina K.L., Riblet R., Beau M.M.L., Fisher A.G., and Singh H. Subnuclear compartmentalization of immunoglobulin loci during lymphocyte development. Science 296 (2002) 158-162. This is the first paper demonstrating contraction of the IgH locus upon commitment to the B cells lineage. Additionally, it is shown that the IgH alleles in non-B cells are located at the nuclear membrane, whereas in B cells the IgH alleles are positioned in centrally nuclear domains.
38. Yang Q., Riblet R., and Schildkraut C.L. Sites that direct nuclear compartmentalization are near the 5′ end of the mouse immunoglobulin locus. Mol Cell Biol 25 (2005) 6021-6030
39. Skok J.A., Brown K.E., Azuara V., Caparros M.L., Baxter J., Takacs K., Dillon N., Gray D., Perry R.P., Merkenschlager M., and Fisher A.G. Nonequivalent nuclear location of immunoglobulin alleles in B lymphocytes. Nat Immunol 2 (2001) 848-854
40. Roldan E., Fuxa M., Chong W., Martinez D., Novatchkova M., Busslinger M., and Skok J. Locus 'decontraction' and centromeric recruitment contribute to allelic exclusion of the immunoglobulin heavy-chain gene. Nat Immunol 6 (2005) 31-41
41. Goldmit M., Ji Y., Skok J., Roldan E., Jung S., Cedar H., and Bergman Y. Epigenetic ontogeny of the IgK locus during B cell development. Nat Immunol 6 (2005) 198-203. Here, evidence is provided that in pre-B cells the IgK locus is associated with either active chromatin or centromeric heterochromatin. Interestingly, the interaction with heterochromatin is associated with Ikaros and HP1 binding.
42. Liu Z., Widlak P., Zou P., Xiao F., Oh M., Li S., Chang M.Y., Shay J.W., and Garrard W.T. A recombination silencer that specifies heterochromatin positioning and Ikaros association in the immunoglobulin K locus. Immunity 24 (2006) 405-415. The investigators identify a novel regulatory element, named Sis, required for the targeting of the IgK locus to centromeric heterochromatin. It is proposed that Sis is involved in the mono-allelic IgK silencing.
43. Sayegh C., Jhunjhunwala S., Riblet R., and Murre C. Visualization of looping involving the immunoglobulin heavy-chain locus in developing B cells. Genes Dev 19 (2005) 322-327
44. Park M., and Atchinson M.I. Isolation of a candidate repressor/activator, NF-E1 (YY1), that binds to the immunoglobulin K 3′ enhancer and the immunoglobulin heavy chain mE1 site. Proc Natl Acad Sci 88 (1991) 9804-9808
45. Gordon S.J., Saleque S., and Birnstein B.K. Yin Yang is a lipopolysaccharide-inducible activator of the murine 3′ Igh enhancer, hs3. J Immunol 170 (2003) 5549-5557
46. Calame K., and Atchison M. YY1 helps to bring loose ends together. Genes Dev 15 (2007) 1145-1152
47. Liang H.E., Hsu L.Y., Cado D., and Schlissel M.S. Variegated transcriptional activation of the immunoglobulin K locus in pre-B cells contributes to the allelic exclusion of light-chain expression. Cell 118 (2004) 19-29
48. Skok J.A., Gisler R., Novatchkova M., Farmer D., de Laat W., and Busslinger M. Reversible contraction by looping of the Tcrα and Tcrβ loci in rearranging thymocytes. Nat Immunol 8 (2007) 378-387. Previous data obtained by the investigators have demonstrated that the IgH alleles undergo de-contraction upon developing into the pre-B cell compartment. The studies described in this paper extend these observations to the TCR loci. The TCRβ and TCRα loci underwent long-range contraction in the DP and DN compartment, respectively. It is suggested that locus de-contraction contributes to the allelic exclusion mechanism of TCR genes.
49. Bain G., Romanow W.J., Albers K., Havran W.L., and Murre C. Positive and negative regulation of V(D)J recombination by the E2A proteins. J Exp Med 189 (1999) 289-300