Recent advances in our understanding of the three-dimensional organization of 
the eukaryotic nucleus have rendered the spatial distribution of genes 
increasingly relevant. In a recent work (Tsochatzidou et al., Nucleic Acids Res 
45:5818-5828, 2017), we proposed the existence of a functional 
compartmentalization of the yeast genome according to which, genes occupying the 
chromosomal regions at the nuclear periphery have distinct structural, 
functional and evolutionary characteristics compared to their 
centromeric-proximal counterparts. Around the same time, it was also shown that 
the genome of Saccharomyces cerevisiae is organized in topologically associated 
domains (TADs), which are largely associated with the replication timing. In 
this work, we proceed to investigate whether such units of three-dimensional 
genomic organization can be linked to transcriptional activity as a driving 
force for the shaping of genomic architecture. Through the application of a 
simple boundary-calling criterion in genome-wide 3C data, we define ~100 
TAD-like domains which can be clustered in six different classes with radically 
different nucleosomal organizations, significant variations in transcription 
factor binding and uneven chromosomal distribution. Approximately ~20% of the 
genome is found to be confined in regions with "closed" chromatin structure 
around gene promoters. Most interestingly, we find both "open" and "closed" 
regions to be segregated, in the sense that they tend to avoid inter-chromosomal 
interactions. Our data further enforce the notion of a marked 
compartmentalization of the yeast genome in isolated territories, with 
implications in its function and evolution.