MORC1 coordinates TRIM28 interaction and nuclear condensate formation for transposon silencing.

MORC1-mediated transposon repression involves DNA methylation and H3K9me3 deposition, yet the underlying mechanism remains unclear. Here, we show that MORC1 assembles discrete nuclear bodies in gonocytes and, using a doxycycline-inducible NIH3T3 cell system, define two properties: MORC1 drives nuclear condensate formation through an intrinsically disordered region (IDR) containing a bipartite nuclear localization signal, and MORC1 binds TRIM28, a corepressor that recruits the H3K9 methyltransferase SETDB1, and concentrates it within these bodies through protein-protein interactions. An IDR-deficient MORC1 mutant fails to form nuclear condensates but retains TRIM28 binding. Chromatin immunoprecipitation sequencing (ChIP-seq) reveals that this mutant occupies heterochromatin-embedded transposons more strongly than wild-type MORC1, particularly evolutionarily young subfamilies overlapping endogenous MORC1 targets. Notably, exogenous MORC1 forms substantially larger condensates than endogenous MORC1 in gonocytes, and fluorescence recovery after photobleaching (FRAP) analysis shows that MORC1 condensates limit diffusion. We propose a model in which MORC1 function is shaped by coordinated TRIM28 interaction and quantitatively restrained, IDR-dependent condensate formation.