Phase separation of Mer2 organizes the meiotic loop-axis structure of chromatin during meiosis I

Abstract

Sexually reproducing organisms acquire genetic diversity through meiotic recombination during meiosis I, which is initiated via programmed DNA double-strand breaks (DSBs) induced by Spo11-containing machinery in each meiotic cell. The combination of programmed DSB sites in each meiotic cell must be diverse, which requires a certain degree of randomness in the distribution of DSBs. The formation of programmed DSBs requires a preestablished loop-axis structure of chromatin. Here, we demonstrate that the axial element protein Mer2 undergoes liquid-liquid phase separation in vitro and in vivo through its intrinsically disordered C-terminal domain. A DNA binding motif within its central domain is responsible for bringing DNA into Mer2 liquid droplets and Mer2-DNA complex could assemble into filamentous structures extending from the droplets. These results suggest that phase separation of Mer2 drives the formation of a droplet-loop structure of meiotic chromatin to facilitate and to diversify programmed DSB formation.