The Gene-Silencing Protein MORC-1 Topologically Entraps DNA and Forms Multimeric Assemblies to Cause DNA Compaction

Microrchidia (MORC) ATPases are critical for gene silencing and chromatin compaction in multiple eukaryotic systems, but the mechanisms by which MORC proteins act are poorly understood. Here, we apply a series of biochemical, single-molecule, and cell-based imaging approaches to better understand the function of the Caenorhabditis elegans MORC-1 protein. We find that MORC-1 binds to DNA in a length-dependent but sequence non-specific manner and compacts DNA by forming DNA loops. MORC-1 molecules diffuse along DNA but become static as they grow into foci that are topologically entrapped on DNA. Consistent with the observed MORC-1 multimeric assemblies, MORC-1 forms nuclear puncta in cells and can also form phase-separated droplets in vitro. We also demonstrate that MORC-1 compacts nucleosome templates. These results suggest that MORCs affect genome structure and gene silencing by forming multimeric assemblages to topologically entrap and progressively loop and compact chromatin. [Display omitted] •Caenorhabditis elegans MORC-1 traps DNA loops•Recruitment of additional MORC-1s cause further loop trapping and DNA compaction•MORC-1 assemblages become topologically entrapped on DNA•MORC-1 forms discrete foci in vivo and can phase transition in vitro MORC proteins in plants and animals regulate the compaction of chromatin, but the molecular mechanism is unknown. Kim et al. demonstrate that the Caenorhabditis elegans MORC-1 dimers can directly compact DNA by topologically entrapping DNA loops. Multiple MORC-1 dimers can also interact to form discrete foci of compacted DNA.