Transcription dependent generation of a specialized chromatin structure at the TCRb locus

V(D)J recombination assembles antigen receptor (AR) 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, in order 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. Here, we highlight a specialized epigenetic marking characterized by high and extended H3K4me3 levels throughout the Db-Jb-Cb 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 DJCb clusters are highly enriched for Ser5-phosphorylated Pol II and short-RNA transcripts, two hallmarks of transcription initiation and early transcription. Interestingly, these features are shared with few other tissue specific genes. We propose that the entire DJCb regions behave as transcription “initiation” platforms, therefore linking a specialized mechanism of Pol II transcription with extended H3K4 trimethylation and highly accessible Db and Jb gene segments. Overall design: Genome-wide analysis via ChIP-Seq for RNA Pol II Ser5-phosphorylated binding in RAG2 -/- thymocytes.