Linking DNA-packing density distribution and TAD boundary locations

“…Studies show that the synergistic action of CTCF and cohesin can form chromatin loops through directional sliding, blocking or promoting distal enhancer-promoter interactions. This process is particularly critical for the stochastic activation of neural development genes ( 85 , 86 ). Chromatin compartments are important functional units of 3D genome organization.…”

“…In mouse ESCs, loss of KLF4 disrupts the proper formation of E-P loops, resulting in abnormal activation of genes that inhibit neural differentiation, ultimately impairing the neuronal differentiation process [ 129 ]. Beyond chromatin loops, the reinforcement of TAD boundaries during early T cell differentiation effectively insulates aberrant E-P interactions and maintains the expression of key lineage-specific transcription factors, thereby safeguarding the T cell differentiation program [ 130 ]. Notably, approximately 10–40% of TAD boundaries exhibit cell-type specificity during human ESC differentiation, suggesting that remarkable reorganization of these structures throughout this process [ 131 ].…”

“…[ 10 ] Within TADs, chromatin fragments interact closely, forming independent structural units. [ 11 ] Chromatin loops are regions of high interaction frequency, further subdivided within TADs. It includes long‐range chromosomal interactions (e.g., loops between promoters and distant enhancers) and short‐range chromosomal interactions.…”