Transcription-Dependent Generation of a Specialized Chromatin Structure at the TCRβ Locus

The Journal of Immunology, 2015, doi: 10.4049/​jimmunol.1400789, vol. 194 no. 7, 3432-3443 published on 02.03.2015
The Journal of Immunology, online article
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 Ser5-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.

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