Molecular mechanisms for environmentally induced plasticity in the positioning of meiotic recombination at hotspots

In meiosis, Spo11/Rec12-initiated homologous recombination is clustered at hotspots that regulate its frequency and distribution across the genome. Intriguingly, the intensities and positions of recombination hotspots can change dramatically in response to intracellular and extracellular conditions, and can display epigenetic memory. Here, using the fission yeast Schizosaccharomyces pombe, we reveal mechanisms for hotspot plasticity. We show that each of six hotspot-activating proteins (transcription factors Atf1, Pcr1, Php2, Php3, Php5, Rst2) is rate-limiting for promoting recombination at its own DNA binding site, allowing each class of hotspot to be regulated independently by agonistic and antagonistic signals. We also discovered that the regulatory protein-DNA complexes can establish a recombinationally poised epigenetic state before meiosis. Notably, Atf1 and Pcr1 controlled the activation of DNA sequence-dependent hotspots to which they do not bind; and they do so by regulating the expression of other hotspot-activating proteins. Thus, while each transcription factor activates its own class of DNA sequence-dependent hotspots directly in cis, cross-talk between regulatory networks modulates in trans the frequency and positioning of recombination at other classes of DNA sequence-dependent hotspots. We posit that such mechanisms allow cells to alter the frequency distribution of meiotic recombination in response to metabolic states and environmental cues.