Eukaryotic topoisomerase II (topo II) is the essential decatenase of newly 
replicated chromosomes and the main relaxase of nucleosomal DNA. Apart from 
these general tasks, topo II participates in more specialized functions. In 
mammals, topo IIα interacts with specific RNA polymerases and 
chromatin-remodeling complexes, whereas topo IIβ regulates developmental genes 
in conjunction with chromatin remodeling and heterochromatin transitions. Here 
we show that in budding yeast, topo II regulates the expression of specific gene 
subsets. To uncover this, we carried out a genomic transcription run-on shortly 
after the thermal inactivation of topo II. We identified a modest number of 
genes not involved in the general stress response but strictly dependent on topo 
II. These genes present distinctive functional and structural traits in 
comparison with the genome average. Yeast topo II is a positive regulator of 
genes with well-defined promoter architecture that associates to chromatin 
remodeling complexes; it is a negative regulator of genes extremely 
hypo-acetylated with complex promoters and undefined nucleosome positioning, 
many of which are involved in polyamine transport. These findings indicate that 
yeast topo II operates on singular chromatin architectures to activate or 
repress DNA transcription and that this activity produces functional responses 
to ensure chromatin stability.