Transcription-dependent generation of a specialized chromatin structure at the TCRβ locus.
V(D)J recombination assembles Ag receptor genes during lymphocyte development. Enhancers at AR loci are known to control V(D)J recombination at associated alleles, in part by increasing chromatin accessibility of the locus, to allow the recombination machinery to gain access to its chromosomal substrates. However, whether there is a specific mechanism to induce chromatin accessibility at AR loci is still unclear. In this article, we highlight a specialized epigenetic marking characterized by high and extended H3K4me3 levels throughout the Dβ-Jβ-Cβ gene segments. We show that extended H3K4 trimethylation at the Tcrb locus depends on RNA polymerase II (Pol II)-mediated transcription. Furthermore, we found that the genomic regions encompassing the two DJCβ clusters are highly enriched for Ser(5)-phosphorylated Pol II and short-RNA transcripts, two hallmarks of transcription initiation and early transcription. Of interest, these features are shared with few other tissue-specific genes. We propose that the entire DJCβ regions behave as transcription "initiation" platforms, therefore linking a specialized mechanism of Pol II transcription with extended H3K4 trimethylation and highly accessible Dβ and Jβ gene segments.
Centre d'Immunologie de Marseille-Luminy, Aix-Marseille University, UM2, 13288 Marseille, France; INSERM, U1104, 13288 Marseille, France; Centre National de la Recherche Scientifique, UMR7280, F-13009 Marseille, France;
Joaquin
J
Zacarías-Cabeza
INSERM U1090, Technological Advances for Genomics and Clinics, F-13009 Marseille, France; Aix-Marseille University, UMR-S 1090, Technological Advances for Genomics and Clinics, F-13009 Marseille, France;
Mohamed
M
Belhocine
INSERM U1090, Technological Advances for Genomics and Clinics, F-13009 Marseille, France; Aix-Marseille University, UMR-S 1090, Technological Advances for Genomics and Clinics, F-13009 Marseille, France;
Laurent
L
Vanhille
Centre d'Immunologie de Marseille-Luminy, Aix-Marseille University, UM2, 13288 Marseille, France; INSERM, U1104, 13288 Marseille, France; Centre National de la Recherche Scientifique, UMR7280, F-13009 Marseille, France; INSERM U1090, Technological Advances for Genomics and Clinics, F-13009 Marseille, France; Aix-Marseille University, UMR-S 1090, Technological Advances for Genomics and Clinics, F-13009 Marseille, France;
Pierre
P
Cauchy
Centre d'Immunologie de Marseille-Luminy, Aix-Marseille University, UM2, 13288 Marseille, France; INSERM, U1104, 13288 Marseille, France; Centre National de la Recherche Scientifique, UMR7280, F-13009 Marseille, France;
Frederic
F
Koch
Centre d'Immunologie de Marseille-Luminy, Aix-Marseille University, UM2, 13288 Marseille, France; INSERM, U1104, 13288 Marseille, France; Centre National de la Recherche Scientifique, UMR7280, F-13009 Marseille, France;
Aleksandra
A
Pekowska
Centre d'Immunologie de Marseille-Luminy, Aix-Marseille University, UM2, 13288 Marseille, France; INSERM, U1104, 13288 Marseille, France; Centre National de la Recherche Scientifique, UMR7280, F-13009 Marseille, France;
Romain
R
Fenouil
INSERM U1090, Technological Advances for Genomics and Clinics, F-13009 Marseille, France; Aix-Marseille University, UMR-S 1090, Technological Advances for Genomics and Clinics, F-13009 Marseille, France; Transcriptomic and Genomic Marseille-Luminy, Infrastructures en Biologie, Santé et Agronomie, 13288 Marseille, France;
Aurélie
A
Bergon
Centre Nacional D'Anàlisi Genòmica, Parc Científic de Barcelona, Baldiri i Reixac, 08028 Barcelona, Spain;
Marta
M
Gut
Centre Nacional D'Anàlisi Genòmica, Parc Científic de Barcelona, Baldiri i Reixac, 08028 Barcelona, Spain;
Ivo
I
Gut
Department of Molecular Epigenetics, Helmholtz Center Munich, Center for Integrated Protein Science, 80336 Munich, Germany; and.
Dirk
D
Eick
INSERM U1090, Technological Advances for Genomics and Clinics, F-13009 Marseille, France; Aix-Marseille University, UMR-S 1090, Technological Advances for Genomics and Clinics, F-13009 Marseille, France; Transcriptomic and Genomic Marseille-Luminy, Infrastructures en Biologie, Santé et Agronomie, 13288 Marseille, France;
Jean
J
Imbert
Centre d'Immunologie de Marseille-Luminy, Aix-Marseille University, UM2, 13288 Marseille, France; INSERM, U1104, 13288 Marseille, France; Centre National de la Recherche Scientifique, UMR7280, F-13009 Marseille, France; ferrier@ciml.univ-mrs.fr jean-christophe.andrau@igmm.cnrs.fr salvatore.spicuglia@inserm.fr.
Pierre
P
Ferrier
Centre d'Immunologie de Marseille-Luminy, Aix-Marseille University, UM2, 13288 Marseille, France; INSERM, U1104, 13288 Marseille, France; Centre National de la Recherche Scientifique, UMR7280, F-13009 Marseille, France; Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique, UMR5535, 34293 Montpellier, France ferrier@ciml.univ-mrs.fr jean-christophe.andrau@igmm.cnrs.fr salvatore.spicuglia@inserm.fr.
Jean-Christophe
JC
Andrau
Centre d'Immunologie de Marseille-Luminy, Aix-Marseille University, UM2, 13288 Marseille, France; INSERM, U1104, 13288 Marseille, France; Centre National de la Recherche Scientifique, UMR7280, F-13009 Marseille, France; INSERM U1090, Technological Advances for Genomics and Clinics, F-13009 Marseille, France; Aix-Marseille University, UMR-S 1090, Technological Advances for Genomics and Clinics, F-13009 Marseille, France; ferrier@ciml.univ-mrs.fr jean-christophe.andrau@igmm.cnrs.fr salvatore.spicuglia@inserm.fr.
Salvatore
S
Spicuglia
D000818:Animals; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D047369:Chromatin Immunoprecipitation; D019175:DNA Methylation; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D059014:High-Throughput Nucleotide Sequencing; D006657:Histones / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D012319:RNA Polymerase II / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D014158:Transcription, Genetic; D060152:V(D)J Recombination
D002843:Chromatin; D006657:Histones; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012319:RNA Polymerase II