Intranuclear localization of transcription factories and immunoglobulin heavy chain gene alleles during human B-cell maturation

Pichugin, A. V.; Iarovaia, O. V.; Sklyar, I. V.; Lacombe, G.; Razin, S. V.; Fest, T.; Lipinski, M.; Vassetzky, Y. S.

doi:10.7124/bc.00091C

Biopolym. Cell. 2016; 32(3):179-183.

http://dx.doi.org/10.7124/bc.00091C

Structure and Function of Biopolymers

Intranuclear localization of transcription factories and immunoglobulin heavy chain gene alleles during human B-cell maturation

1, 2, 3Pichugin A. V., 1, 2, 4Iarovaia O. V., 1, 2, 4Sklyar I. V., 5Lacombe G., 2, 4, 5Razin S. V., 5Fest T., 1, 2Lipinski M., 1, 2Vassetzky Y. S.

CNRS UMR 8126, Universit Paris-Sud 11, Institut Gustave Roussy
114, rue Edouard Vaillant, Villejuif, France, 94805
LIA 1066 French-Russian Joint Cancer Research Laboratory
Villejuif, France–Moscow, Russian Federation
Peter the Great St. Petersburg Polytechnic University
29, Polytechnicheskaya Str, St. Petersburg, Russian Federation, 195251
Institute of Gene Biology, Russian Academy of Sciences
34/5, Vavilova Str., Moscow, Russian Federation, 119334
INSERM U917, Université de Rennes
2, avenue du Professeur Léon Bernard, F - 35043 Rennes, France
Faculty of Biology, M. V. Lomonosov Moscow State University
Leninskie Gory, Moscow, Russian Federation, 119991

Abstract

Immunoglobulin heavy chain (IGH) gene locus is expressed monoallelically in human B cells. Aim. To study the role of nuclear organization in regulation of the IGH expression during B-cell differentiation. Methods. Immunofluorescence in situ hybridization on 3D-preserved nuclei (3D immuno-FISH). Results. Active RNA polymerase II (Pol II) molecules and the IGH locus were detected in the periphery of the nucleoli at some stages of B-cell differentiation. Conclusions. We observed significant changes in the pattern of distribution of RNA polymerase II in the nucleus during B-cell differentiation, but no preferential co-localization of the productive IGH allele with the transcription factories in the vicinity of the nucleolus and in the nucleoplasm was observed.

Keywords: Immunoglobulin heavy chain gene, transcription, nucleolus, B-cell maturation

Full text: (PDF, in English)

References

[1] Razin SV, Vassetzky YS. 3D genomics imposes evolution of the domain model of eukaryotic genome organization. Chromosoma. 2016 Jun 10.

[2] Razin SV, Gavrilov AA, Pichugin A, Lipinski M, Iarovaia OV, Vassetzky YS. Transcription factories in the context of the nuclear and genome organization. Nucleic Acids Res. 2011;39(21):9085-92.

[3] Hosokawa Y, Arnold A. Mechanism of cyclin D1 (CCND1, PRAD1) overexpression in human cancer cells: analysis of allele-specific expression. Genes Chromosomes Cancer. 1998;22(1):66-71.

[4] Rajewsky K. Clonal selection and learning in the antibody system. Nature. 1996;381(6585):751-8.

[5] 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. RAG-1 and ATM coordinate monoallelic recombination and nuclear positioning of immunoglobulin loci. Nat Immunol. 2009;10(6):655-64.

[6] Kosak ST, Skok JA, Medina KL, Riblet R, Le Beau MM, Fisher AG, Singh H. Subnuclear compartmentalization of immunoglobulin loci during lymphocyte development. Science. 2002;296(5565):158-62.

[7] Skok JA, Brown KE, Azuara V, Caparros ML, Baxter J, Takacs K, Dillon N, Gray D, Perry RP, Merkenschlager M, Fisher AG. Nonequivalent nuclear location of immunoglobulin alleles in B lymphocytes. Nat Immunol. 2001;2(9):848-54.

[8] Sklyar I, Iarovaia OV, Gavrilov AA, Pichugin A, Germini D, Tsfasman T, Caron G, Fest T, Lipinski M, Razin SV, Vassetzky YS. Distinct Patterns of Colocalization of the CCND1 and CMYC Genes With Their Potential Translocation Partner IGH at Successive Stages of B-Cell Differentiation. J Cell Biochem. 2016;117(7):1506-10.

[9] Allinne J, Pichugin A, Iarovaia O, Klibi M, Barat A, Zlotek-Zlotkiewicz E, Markozashvili D, Petrova N, Camara-Clayette V, Ioudinkova E, Wiels J, Razin SV, Ribrag V, Lipinski M, Vassetzky YS. Perinucleolar relocalization and nucleolin as crucial events in the transcriptional activation of key genes in mantle cell lymphoma. Blood. 2014;123(13):2044-53.

[10] Ulianov SV, Gavrilov AA, Razin SV. Nuclear compartments, genome folding, and enhancer-promoter communication. Int Rev Cell Mol Biol. 2015;315:183-244.

[11] Le Gallou S, Caron G, Delaloy C, Rossille D, Tarte K, Fest T. IL-2 requirement for human plasma cell generation: coupling differentiation and proliferation by enhancing MAPK-ERK signaling. J Immunol. 2012;189(1):161-73.

[12] Politz JC, Scalzo D, Groudine M. The redundancy of the mammalian heterochromatic compartment. Curr Opin Genet Dev. 2016;37:1-8.

[13] Schlissel MS. Regulating antigen-receptor gene assembly. Nat Rev Immunol. 2003;3(11):890-9.

[14] Daly J, Licence S, Nanou A, Morgan G, Mårtensson IL. Transcription of productive and nonproductive VDJ-recombined alleles after IgH allelic exclusion. EMBO J. 2007;26(19):4273-82.

[15] Vettermann C, Schlissel MS. Allelic exclusion of immunoglobulin genes: models and mechanisms. Immunol Rev. 2010;237(1):22-42.

[16] Snider L, Asawachaicharn A, Tyler AE, Geng LN, Petek LM, Maves L, Miller DG, Lemmers RJ, Winokur ST, Tawil R, van der Maarel SM, Filippova GN, Tapscott SJ. RNA transcripts, miRNA-sized fragments and proteins produced from D4Z4 units: new candidates for the patophysiology of facioscapulohumeral dystrophy. Hum Mol Genet. 2009;18(13):2414-30.

[17] Woo CJ, Martin A, Scharff MD. Induction of somatic hypermutation is associated with modifications in immunoglobulin variable region chromatin. Immunity. 2003;19(4):479-89.

[18] Hanakahi LA, Maizels N. Transcriptional activation by LR1 at the Emu enhancer and switch region sites. Nucleic Acids Res. 2000;28(14):2651-7.