PT  - JOURNAL ARTICLE
AU  - Stephen Henderson
AU  - Venu Pullabhatla
AU  - Arnulf Hertweck
AU  - Emanuele de Rinaldis
AU  - Javier Herrero
AU  - Graham M Lord
AU  - Richard G Jenner
TI  - The Th1 cell regulatory circuitry is largely conserved between human and mouse
AID  - 10.26508/lsa.202101075
DP  - 2021 Nov 01
TA  - Life Science Alliance
PG  - e202101075
VI  - 4
IP  - 11
4099  - https://www.life-science-alliance.org/content/4/11/e202101075.short
4100  - https://www.life-science-alliance.org/content/4/11/e202101075.full
SO  - Life Sci. Alliance2021 Nov 01; 4
AB  - 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.