Initiation of Meiotic Homologous Recombination: Flexibility, Impact of Histone Modifications, and Chromatin Remodeling

Meiotic recombination is initiated by the formation of DNA double-strand breaks (DSBs) catalyzed by the evolutionary conserved Spo11 protein and accessory factors. DSBs are nonrandomly distributed along the chromosomes displaying a significant (~400-fold) variation of frequencies, which ultimately establishes local and long-range "hot" and "cold" domains for recombination initiation. This remarkable patterning is set up within the chromatin context, involving multiple layers of biochemical activity. Predisposed chromatin accessibility, but also a range of transcription factors, chromatin remodelers, and histone modifiers likely promote local recruitment of DSB proteins, as well as mobilization, sliding, and eviction of nucleosomes before and after the occurrence of meiotic DSBs. Here, we assess our understanding of meiotic DSB formation and methods to change its patterning. We also synthesize current heterogeneous knowledge on how histone modifications and chromatin remodeling may impact this decisive step in meiotic recombination.