Differentiation of effector CD4 T cell populations (*) - PubMed (original) (raw)

Figure 4

Important _cis_-regulatory elements at the Ifng, Il4/Il13, and Il17a/Il17f loci and binding of transcription factors to these sites. (a) Within ~140 kb flanking the Ifng gene, many conserved noncoding sequences and their epigenetic modifications have been studied (259). CNS–22 has been shown to be critical for IFN-γ production (261). Many transcription factors, including T-bet, STAT4, Runx3, STAT5, and CTCF, bind to different regions of the Ifng gene (65, 131, 144, 181, 243, 261, 262). Our unpublished data suggest that Runx3 also binds to other regulatory elements in addition to the Ifng promoter. (b) Within ~70 kb flanking the Il4/Il13 genes, several important regulatory elements, including the locus control region (LCR), CNS1, Il4 HSII, Il4 HSIV, and Il4 HSVA/V, have been identified (, , –267). Many transcription factors, including GATA3, c-Maf, STAT5, STAT6, Runx3, NFAT, and Notch/CSL, directly bind to different regions of the Il4/Il13 locus (61, 62, 122, 137, 144, 165, 233). Our unpublished data obtained from anti-GATA3 ChIPseq showed six GATA3-binding sites across this ~70-kb region in Th2 cells, with three located in LCR at RHS4, 5, and 6 and the other three at ~1.6 kb upstream of Il13, Il4 HSII, and Il4 HSVA. (c) Epigenetic modifications of the CNSs across ~160 kb of Il17a/Il17f have been reported (268). Some transcription factors critical for regulation of IL-17 expression, including RORγt, STAT3, BATF, Runx1, NFAT, and Gfi-1/LSD1, directly bind to the CNS or promoter regions of Il17a/Il17f (90, 110, 152, 160, 177, 205).