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Molecular and genetic definitions of human-specific changes to genomicregulatory networks (GRNs) contributing to development of unique to humanphenotypes remain a highly significant challenge. Genome-wide proximityplacement analysis of diverse families of human-specific genomic regulatoryloci (HSGRL) identified topologically-associating domains (TADs) that aresignificantly enriched for HSGRL and designated rapidly-evolving in humans TADs(Genome Biol Evol. 2016 8; 2774-88). Here, the analysis of HSGRL, hESC-enrichedenhancers, super-enhancers (SEs), and specific sub-TAD structures termedsuper-enhancer domains (SEDs) has been performed. Markedly distinct features ofthe principal regulatory structures of interphase chromatin evolved in the hESCgenome compared to mouse: the SED quantity is 3-fold higher and the median SEDsize is significantly larger. Concomitantly, the overall TAD quantity isincreased by 42% while the median TAD size is significantly decreased (p =9.11E-37) in the hESC genome. Present analyses illustrate a putative globalrole for HSGRL in shaping the human-specific features of the interphasechromatin organization and functions, which are facilitated by acceleratedcreation of new enhancers associated with targeted placement of HSGRL atdefined genomic coordinates. A trend toward the convergence of TAD and SEDarchitectures of interphase chromatin in the hESC genome may reflect changes of3D-folding patterns of linear chromatin fibers designed to enhance bothregulatory complexity and functional precision of GRNs by creatingpredominantly a single gene per regulatory domain structures.

Role of distal enhancers in shaping 3D-folding patterns and defining  human-specific features of interphase chromatin architecture in embryonic  stem cells