Fig. 2: Tissue-specific enhancer forms local self-interacting chromatin domains.

a, 4C-seq contact profiles plotted as overlays, comparing contacts of the integrated reporter gene promoter (P) in a cell line lacking the enhancer (no E, in blue), versus contacts of the corresponding endogenous genomic position (pos0) in wild-type (WT, in dark gray) K562 cells. Shared contacts are in light grey. y axis: 4C coverage per 1 million cis-reads. VP: 4C-seq viewpoint. The track below the graph shows the differential 4C-seq signal (DC: differential contacts), with contacts gained and lost by the gene promoter in blue and gray, respectively. n = 2 technical replicates/clone. b, 4C-seq profile overlays comparing contacts of the integrated promoter (P) in the different E-lines (green profiles), versus those of the integrated promoter in the cell line lacking an integrated enhancer (no E: dark gray profiles). Differential contacts are plotted below each overlay profile. Bottom, CTCF and SMC3 ChIP–seq tracks. c, 4C-seq differential contacts tracks showing, per E-line (E0, E11, E47 and E100), the gained (green) and lost (gray) contacts of the gene promoter (P) as compared with its contacts measured by 4C-seq in the cell line lacking the enhancer (top), as well as the gained (orange) and lost (gray) contacts of the enhancer (bottom), as compared with the contacts of its corresponding endogenous chromosomal position (pos0, pos11, pos47 and pos100, respectively) in the cell line lacking the enhancer. For reference, the aligned HiC contact map is shown on top. d, Same as in c, but for the E407 cell line. SMC3 and CTCF ChIP–seq signal and CTCF-site orientations are indicated at the bottom. e, 4C-seq overlay contact profiles showing gene promoter contacts gained (green) and lost (black) upon integration of the enhancer at position E407, as compared with its contacts in a cell line carrying no integrated enhancer.