Dexamethasone increases H3K27Ac levels and promoter/enhancer interactions in canonical GC-regulated genes in human T-ALL cells. H3K27Ac Hi-ChIP tracks (top) showing interaction between H3K27Ac regions in canonical GC target genes PIK3IP1 (A), FKBP5 (B), TSC22D3 (C), and BCL2L11 (D), treated with DMSO (pink track) or dexamethasone (blue track). Black lines indicate the anchors of interaction. Virtual 4C extract from Hi-ChIP (bottom) shows interaction frequency from the viewpoint (red highlight) of GC target genes PIK3IP1 (A), FKBP5 (B), TSC22D3 (C), and BCL2L11 (D), treated with DMSO (yellow) or dexamethasone (blue). ESRRB binding sites were determined using the ERRE consensus site AAGGTCA. GR binding sites were determined using published ChIP sequencing data in T-ALL patient samples.³⁹  (E) Hi-ChIP data for BCL2L11 was used to model ESRRB regulation of GC-induced gene expression. Dexamethasone triggered GR and ESRRB and coactivator binding to the BCL2L11 enhancer (red) which looped back to the promoter (green) to recruit RNA polymerase II and the transcription initiation complex, thereby inducing BCL2L11 expression.