RT Journal Article
SR Electronic
T1 The Th1 cell regulatory circuitry is largely conserved between human and mouse
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202101075
DO 10.26508/lsa.202101075
VO 4
IS 11
A1 Stephen Henderson
A1 Venu Pullabhatla
A1 Arnulf Hertweck
A1 Emanuele de Rinaldis
A1 Javier Herrero
A1 Graham M Lord
A1 Richard G Jenner
YR 2021
UL https://www.life-science-alliance.org/content/4/11/e202101075.abstract
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.