The CEBPA promoter contacts multiple intra-TAD genomic sites. Stronger interaction with a 21-kb genomic region in CEBPA-expressing myeloid cells. (A) HI-C heatmap matrix (25-kb resolution) in the K562 cell line on chromosome 19 reveals a 170-kb CEBPA TAD (2), which is flanked by TADs 1 and 3. The CEBPA TAD also contains CEBPG and part of SLC7A10. (B) Normalized 4C-seq profiles of myeloid CEBPA⁺ HL-60 (blue), lymphoid CEBPA⁻ Jurkat (red) and cervical CEBPA⁻ HeLa (green) cell lines. The viewpoint (red triangle) located at the CEBPA promoter shows multiple interacting sites confined to the CEBPA-TAD (borders marked in gray). (C) CTCF ChIP-seq (ENCODE) in the myeloid HL-60, lymphoid Jurkat, and cervical HeLa cell lines shows enrichment at the CEBPA TAD borders (gray) which overlap with the HI-C contact-matrix borders separating the CEBPA-containing TAD2 from TAD1 and TAD3. (D) Semiquantitative analysis of 4C-seq data to distinguish interacting regions occurring at higher contact frequencies in CEBPA⁺ myeloid cells (orange; n = 3) compared with CEBPA⁻ cells (blue; n = 3). The CEBPA viewpoint is marked with a dotted line. A specific region indicated in gray of around 21 kb located 3′ of CEBPA and with >250 reads per million shows a statistically significant higher contact frequency (FDR < 0.05) in CEBPA⁺ as compared with CEBPA⁻ cell lines.