Ubiquitination condensates sculpt genome architecture via non-enzymatic chromatin mechanics

Non-enzymatic condensates may bridge distal loci, while enzymatic ones modulate histone modifications by locally concentrating reactants. The scaffold protein Lge1 and the E3 ligase Bre1 form layered condensates that promote histone H2B ubiquitination.

Here we show that these ubiquitination condensates generate mechanical forces, reshaping gene body topology in relation to promoter and terminator regions, independently of histone H2B ubiquitination. Single-molecule biophysics reveals that the CoRE (Condensate Regulatory Element) of Lge1 governs DNA entry into condensates and mechanical force generation in vitro. Micro-C shows that CoRE residues are required to maintain gene body architecture in vivo, coupling condensate mechanics to specific transcriptional outcomes and cellular fitness.