CCR4 is a transcriptional target of ETS1 in NA-ATLL. (A) CCR4 gene map of chromatin accessibility and ETS1 binding motifs. Purple, NA-ATLL specific chromatin accessibility (ATAC-seq); Lollipops, predicted ETS1 binding sites within open chromatin region; Green, exons. (B) NA-ATLL–specific chromatin accessibility over CCR4 TSS region. ATAC-seq data shown for NA-ATLL, J-ATLL, and normal Treg cells. (C) ETS1 binding to the CCR4 promoter region corresponding to chromatin accessibility site was confirmed by analysis of ETS1 ChIP-seq data in Treg cells. (D) ETS1 expression in NA-ATLL and J-ATLL cell lines (mean ± SE; 2-sided t test) and primary NA-ATLL and normal CD4 cells (mean ± SE; FDR-adjusted P value). TPM, transcripts per million. (E) CCR4 and ETS1 expression are highly correlated in NA-ATLL cell lines (P < .001; R = 0.995) and NA-ATLL primary cells (P = .026; R = 0.662). Pearson correlation; TPM, transcripts per million. (F) siRNA knockdown of ETS1 resulted in decreased CCR4 expression (P = .021). ATL18 cell line; 2-sided t test, mean ± standard deviation. Data are representative of 3 separate transfections. (G-H) ETS1 and CCR4 expression stratified by CCR4 mutation status in NA-ATLL primary tumor cells. Mean ± standard deviation, 2-sided t test.