1. The Th1 cell regulatory circuitry is largely conserved between human and mouse.
- Author
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Henderson S, Pullabhatla V, Hertweck A, de Rinaldis E, Herrero J, Lord GM, and Jenner RG
- Subjects
- Animals, Binding Sites genetics, Databases, Genetic, Gene Expression genetics, Genome genetics, Humans, Mice, Protein Binding genetics, T-Box Domain Proteins metabolism, Th1 Cells immunology, Transcription Factors genetics, Transcription Factors physiology, Transcriptome genetics, Gene Expression Regulation genetics, T-Box Domain Proteins genetics, Th1 Cells physiology
- Abstract
Gene expression programs controlled by lineage-determining transcription factors are often conserved between species. However, infectious diseases have exerted profound evolutionary pressure, and therefore the genes regulated by immune-specific transcription factors might be expected to exhibit greater divergence. T-bet (Tbx21) is the immune-specific, lineage-specifying transcription factor for T helper type I (Th1) immunity, which is fundamental for the immune response to intracellular pathogens but also underlies inflammatory diseases. We compared T-bet genomic targets between mouse and human CD4
+ T cells and correlated T-bet binding patterns with species-specific gene expression. Remarkably, we found that the majority of T-bet target genes are conserved between mouse and human, either via preservation of binding sites or via alternative binding sites associated with transposon-linked insertion. Species-specific T-bet binding was associated with differences in transcription factor-binding motifs and species-specific expression of associated genes. These results provide a genome-wide cross-species comparison of Th1 gene regulation that will enable more accurate translation of genetic targets and therapeutics from pre-clinical models of inflammatory and infectious diseases and cancer into human clinical trials., (© 2021 Henderson et al.)- Published
- 2021
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