Chromatin domains are encoded and molded by isochores

The formation of mammalian chromatin domains was investigated by analyzing the domain/isochore connection. This showed that LADs correspond to GC-poor isochores and are compositionally flat, flexible chromatin structures because of the local nucleosome depletions associated with the presence of oligo-As. In contrast, TADs correspond to GC-rich isochores that consist of single or (much more frequently) multiple, GC peaks that shape the single or multiple, loops of TADs. Indeed, the increasing nucleosome depletions linked to the GC gradients of isochore peaks lead to an increasing chromatin flexibility (accompanied by an increasing accessibility and decreasing supercoiling). In conclusion, isochores not only encode but also mold chromatin architecture; while architectural proteins play a role in closing and insulating TAD loops. An extension of this model concerns the encoding of open and closed chromosome compartments by alternating GC-rich and GC-poor isochores, the interactions among compartments defining the 3-D chromosome folding.