HIF-1 binding is required for TET3 upregulation in hypoxia. (A) TET3 expression in K562 cells in normoxia vs hypoxia, up to 5 days. (B) Overlay of K562 enhancers with HIF-1α ChIP in normoxia and hypoxia in TET3 genes. The binding sites are highlighted in gray (Sites 1 and 2). (C) Sequences of binding Site 1 and Site 2, as well as positions of CRISPR guides used to delete the binding sites. Core E-box motif (ACGT) is indicated by red letters. PAM sequences (NGG) are indicated by green boxes. (D) TET3 expression in normoxia vs hypoxia in TET3^WT, TET3^ΔS1, TET3^ΔS2, and TET3^ΔS1+S2 clones. N = 2 for HIF-1α ChIP. N = 3 for hypoxia treatment of CRISPRed K562 clones. *P < .05; ***P < .001.