Simulations of the CCND1 region in GM12878 cells. (A) A map of the genes in the vicinity of CCND1 is shown above heat maps for: (i) publicly available Hi-C data for GM12878 cells; and (ii) simulated Hi-C from the same region (obtained from 4400 independent configurations). TAD boundary positions are indicated with blue dashed lines; green dashed lines indicate a “subTAD” region (see text). Some unmappable regions are visible as gaps in the data (white stripes). (B) Simulation snapshots of the 3D structure of the CCND1 region, including the CCND1-TAD (pale orange) and the two neighboring TADs (pale green and pale blue; a 1.3-Mbp section of the 3-Mbp region simulated is shown). One representative snapshot is shown large, with five other smaller examples. Several genes are shown in bright colors, as indicated. For clarity, proteins are not shown. (Inset) The same configuration is shown but colored according to the input data used in the simulation, as indicated by label colors; gene positions are circled. (C) Simulated 4C interaction profiles are shown from four viewpoints (blue triangles; these are positioned at promoters of TPCN2, MYEOV, CCND1, and LTO1, and at a DNase hypersensitive site [DHS] downstream from MYEOV). The height of the orange shaded region represents the relative frequency at which that position interacts with the viewpoint. Data used as simulation input (obtained from ENCODE; see Supplemental Methods and Supplemental Table S3) are shown as colored blocks above the plots. Red blocks indicate DHS, used to infer binding sites for active proteins. Blue and black blocks indicate regions with chromatin states corresponding to polycomb and heterochromatin, respectively, used to infer binding for the corresponding proteins. Yellow blocks indicate regions with chromatin states associated with H3K27ac and indicate regions which have a more open chromatin structure in the model. Orange and purple arrowheads indicate the position and directionality of CTCF sites, used to infer loop extruder anchors. Some features are labeled with numbered arrows as referred to in the text.