text: About 600 regulatory sequences in promoters and about 800 regulatory sequences in enhancers appear to depend on double-strand breaks initiated by topoisomerase 2β (TOP2B) for activation.  The induction of particular double-strand breaks is specific with respect to the inducing signal.  When neurons are activated in vitro, just 22 TOP2B-induced double-strand breaks occur in their genomes.  However, when contextual fear conditioning is carried out in a mouse, this conditioning causes hundreds of gene-associated DSBs in the medial prefrontal cortex and hippocampus, which are important for learning and memory.
  Such TOP2B-induced double-strand breaks are accompanied by at least four enzymes of the non-homologous end joining (NHEJ) DNA repair pathway (DNA-PKcs, KU70, KU80 and DNA LIGASE IV) (see figure). These enzymes repair the double-strand breaks within about 15 minutes to 2 hours.  The double-strand breaks in the promoter are thus associated with TOP2B and at least these four repair enzymes.  These proteins are present simultaneously on a single promoter nucleosome (there are about 147 nucleotides in the DNA sequence wrapped around a single nucleosome) located near the transcription start site of their target gene.
  The double-strand break introduced by TOP2B apparently frees the part of the promoter at an RNA polymerase–bound transcription start site to physically move to its associated enhancer.  This allows the enhancer, with its bound transcription factors and mediator proteins, to directly interact with the RNA polymerase that had been paused at the transcription start site to start transcription.
  Similarly, topoisomerase I (TOP1) enzymes appear to be located at many enhancers, and those enhancers become activated when TOP1 introduces a single-strand break.  TOP1 causes single-strand breaks in particular enhancer DNA regulatory sequences when signaled by a specific enhancer-binding transcription factor.  Topoisomerase I breaks are associated with different DNA repair factors than those surrounding TOP2B breaks.  In the case of TOP1, the breaks are associated most immediately with DNA repair enzymes MRE11, RAD50 and ATR.