Discrete DNA sites regulate global distribution of meiotic recombination

Homologous recombination is induced to high levels in meiosis, is initiated by Spo11-catalyzed DNA double-strand breaks (DSBs) and is clustered at hotspots that regulate its positioning in the genome. Recombination is required for proper chromosome segregation in meiosis and defects in its frequency or positioning cause chromosome mis-segregation and, consequently, congenital birth defects such as Down's syndrome. Therefore, elucidating how meiotic recombination is positioned is of fundamental and biomedical interest. Our integration of historical and contemporary advances in the field, plus the re-analysis of published microarray data on the genome-wide distribution of recombination supports a unifying model for such regulation. We posit that discrete DNA sequence motifs position and regulate essentially all recombination across the genome, in much the same way that DNA sites position and regulate transcription. Moreover, we illustrate the use of overlapping mechanisms for the regulation of transcription and meiotic recombination. Bound transcription factors induce histone modifications that position recombination at hotspots.