No abstract

Interleukin-12 (IL-12) is a key cytokine for the development of T helper type 1 (Th1) responses; however, naïve CD4 þ T cells do not express IL-12Rb2, and are therefore unresponsive to IL-12. We have examined the mechanisms that control Th1-specific expression of the human IL12Rb2 gene at early time points after T-cell stimulation.We have identified a Th1-specific enhancer element that binds signal transducer and activator of transcription 4 (STAT4) in vivo in developing Th1 but not Th2 cells. T-cell receptor (TCR) signaling induced histone hyperacetylation and recruitment of BRG1, the ATPase subunit of the SWI/SNF-like BAF chromatin remodeling complex, to the IL-12Rb2 regulatory regions and was associated with lowlevel gene transcription at the IL-12Rb2 locus. However, high-level IL-12Rb2 expression required TCR triggering in the presence of IL-12. Our results indicate a synergistic role of TCR-induced chromatin remodeling and cytokineinduced STAT4 activation to direct IL-12Rb2 expression during Th1 cell development.

T-bet is a key regulator controlling Th1 cell development. This factor is not expressed in naive CD4+ T cells, and the mechanisms controlling expression of T-bet are incompletely understood. In this study, we defined regulatory elements at the human T-bet locus and determined how signals originating at the TCR and at cytokine receptors are integrated to induce chromatin modifications and expression of this gene during human Th1 cell differentiation. We found that T cell activation induced two strong DNase I-hypersensitive sites (HS) and rapid histone acetylation at these elements in CD4+ T cells. Histone acetylation and T-bet expression were strongly inhibited by cyclosporine A, and we detected binding of NF-AT to a HS in vivo. IL-12 and IFN-γ signaling alone were not sufficient to induce T-bet expression in naive CD4+ T cells, but enhanced T-bet expression in TCR/CD28-stimulated cells. We detected a third HS 12 kb upstream of the mRNA start site only in developing Th1 cells, which was bound by IL-12-induced STAT4. Our data suggest that T-bet locus remodeling and gene expression are initiated by TCR-induced NF-AT recruitment and amplified by IL-12-mediated STAT4 binding to distinct distal regulatory elements during human Th1 cell differentiation.

Background: The yellow mealworm beetle, Tenebrio molitor, is a promising alternative protein source for animal and human nutrition and its farming involves relatively low environmental costs. For these reasons, its industrial scale production started this century. However, to optimize and breed sustainable new T. molitor lines, the access to its genome remains essential. Methods: By combining Oxford Nanopore and Illumina Hi-C data, we constructed a high-quality chromosome-scale assembly of T. molitor. Then, we combined RNA-seq data and available coleoptera proteomes for gene prediction with GMOVE. Results: We produced a high-quality genome with a N50 = 21.9Mb with a completeness of 99.5% and predicted 21,435 genes with a median size of 1,780 bp. Gene orthology between T. molitor and Tribolium castaneaum showed a highly conserved synteny between the two coleoptera and paralogs search revealed an expansion of histones in the T. molitor genome. Conclusions: The present genome will greatly help fundamental and applied research such as genetic breeding and will contribute to the sustainable production of the yellow mealworm.

Background: The yellow mealworm beetle, Tenebrio molitor, is a promising alternative protein source for animal and human nutrition and its farming involves relatively low environmental costs. For these reasons, its industrial scale production started this century. However, to optimize and breed sustainable new T. molitor lines, the access to its genome remains essential. Methods: By combining Oxford Nanopore and Illumina Hi-C data, we constructed a high-quality chromosome-scale assembly of T. molitor. Then, we combined RNA-seq data and available coleoptera proteomes for gene prediction with GMOVE. Results: We produced a high-quality genome with a N50 = 22Mb with a completeness of 99.5% and predicted 21,435 genes with a median size of 1,780 bp. Gene orthology between T. molitor and Tribolium castaneaum showed a highly conserved synteny between the two coleoptera. Conclusions: The present genome will greatly help fundamental and applied research such as genetic breeding and will contribute to the sustainable production of the yellow mealworm.