Fig. 1

Hierarchical chromatin organization. Top tier: higher-order compartments A and B, where A is an active compartment and B is an inactive or densely packed compartment (beige-colored top-most triangles). Moving downward, topologically associated domains (TADs) are organized into increasingly higher-resolution structures. Second tier: representative metaTAD structure (gray-colored triangle), where many TADs together form one metaTAD. Inter-TAD interactions, while more sparse, can be detected. Third tier: TADs (light pink triangle) consist of numerous intra-TAD regulatory loops (small red triangles in TADs). These regulatory loops are major governing factors for differential transcriptional output. In tiers 1–3, triangles represent higher-frequency contacts of the three-dimensional (3D) genome shown in two dimensions (2D). Tier four illustrates how a TAD may look in 3D, comprising intra-TAD regulatory loops. Representative examples of regulatory loops are also shown: one enhancer to multiple promoter interactions, promoter–promoter interactions, and multiple enhancers to one promoter interactions. TAD boundaries are marked by the CTCF–cohesin complex (green pentagon). Intra-TAD elements likely consist of different transcription factors (light green circles) and long non-coding RNA (dark gray circles)