Transcription-dependent generation of a specialized chromatin structure at the TCRbeta locus

Zacarias-Cabeza, J.; Belhocine, M.; Vanhille, L.; Cauchy, P.; Koch, F.; Pekowska, A.; Fenouil, R.; Bergon, A.; Gut, M.; Gut, I.; Eick, D.; Imbert, J.; Ferrier, P.; Andrau, J. C.; Spicuglia, S.

J Immunol

2015-04-01 / vol 194 / pages 3432-43


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 Dbeta-Jbeta-Cbeta 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 DJCbeta 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 DJCbeta regions behave as transcription “initiation” platforms, therefore linking a specialized mechanism of Pol II transcription with extended H3K4 trimethylation and highly accessible Dbeta and Jbeta gene segments.

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1550-6606 (Electronic) 0022-1767 (Linking)


Animals; Mice; *Genetic Loci; *Transcription, Genetic; Chromatin Assembly and Disassembly; Chromatin Immunoprecipitation; Chromatin/*genetics/metabolism; DNA Methylation; Genome-Wide Association Study; High-Throughput Nucleotide Sequencing; Histones/metabolism; Mice, Knockout; Models, Biological; Receptors, Antigen, T-Cell, alpha-beta/*genetics; RNA Polymerase II/metabolism; V(D)J Recombination

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