FIGURE 2.

The hierarchy of higher order chromatin organization based on high throughput chromatin conformation capture (Hi-C). Diagrams are shown of higher order chromatin organization in a hierarchy from the whole CT to A and B compartments to topologically associating domains (TADs)/mbp chromatin domains (CDs) to specific enhancer-promoter interactions A-D, with corresponding schematics of Hi-C visualizations representing interchromosomal interactions, A and B compartmentalization, TADs/CDs, and intra-TAD interactions E-H. The Hi-C technique enables determination of pairwise interaction frequencies between regions of chromatin across the genome (represented as a matrix). A,E, At the highest level, total pairwise interaction frequencies between chromosomes can be determined. A simulated matrix of pairwise CT–CT interactions is shown (red = high frequency, blue = low, and white = intermediate). BF, Within CT, chromatin is organized into open, A, euchromatic or closed, B, heterochromatic, compartments. These compartments are in turn composed of TADs exhibiting a triangular pattern of higher frequency interactions along the diagonal. Seven TADs numbered from 1 to 7 are colored red or blue with respect to whether they are contained within A (blue) or B (red) compartments. An interaction between two TADs within a compartment is demarcated with a Y. C,G, A section of this matrix encompassing TADs 3 to 6 is displayed enlarged (darker blue - high frequency, light blue - low). Local interactions are closer to the diagonal while distal interactions are farther from the diagonal. D,H. Enhancer-promoter interactions are generally contained within TADs. A simulated enhancer-promoter interaction is displayed within TAD number 4. This TAD is enlarged to demonstrate the enhancer at ~11 mbp (pink) interacting with the promoter at ~15 mbp (orange)