Three-dimensional genome structure plays an important role in gene regulation. 
Globally, chromosomes are organized into active and inactive compartments while, 
at the gene level, looping interactions connect promoters to regulatory 
elements. Topologically associating domains (TADs), typically several hundred 
kilobases in size, form an intermediate level of organization. Major questions 
include how TADs are formed and how they are related to looping interactions 
between genes and regulatory elements. Here we performed a focused 5C analysis 
of a 2.8 Mb chromosome 7 region surrounding CFTR in a panel of cell types. We 
find that the same TAD boundaries are present in all cell types, indicating that 
TADs represent a universal chromosome architecture. Furthermore, we find that 
these TAD boundaries are present irrespective of the expression and looping of 
genes located between them. In contrast, looping interactions between promoters 
and regulatory elements are cell-type specific and occur mostly within TADs. 
This is exemplified by the CFTR promoter that in different cell types interacts 
with distinct sets of distal cell-type-specific regulatory elements that are all 
located within the same TAD. Finally, we find that long-range associations 
between loci located in different TADs are also detected, but these display much 
lower interaction frequencies than looping interactions within TADs. 
Interestingly, interactions between TADs are also highly cell-type-specific and 
often involve loci clustered around TAD boundaries. These data point to key 
roles of invariant TAD boundaries in constraining as well as mediating 
cell-type-specific long-range interactions and gene regulation.