The Th1 cell regulatory circuitry is largely conserved between human and mouse.
Stephen HendersonVenu PullabhatlaArnulf HertweckEmanuele de RinaldisJavier HerreroGraham M LordRichard G JennerPublished in: Life science alliance (2021)
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.
Keyphrases
- transcription factor
- genome wide
- gene expression
- endothelial cells
- dna binding
- infectious diseases
- dna methylation
- genome wide identification
- clinical trial
- induced pluripotent stem cells
- single cell
- pluripotent stem cells
- oxidative stress
- copy number
- public health
- small molecule
- autism spectrum disorder
- bioinformatics analysis
- binding protein
- bone marrow
- cell therapy
- multidrug resistant
- open label
- young adults
- gram negative
- mesenchymal stem cells
- reactive oxygen species
- phase iii