Dataset Information

Ubiquitination condensates sculpt genome architecture via non-enzymatic chromatin mechanics

ABSTRACT: Biomolecular condensates are emerging as regulators of genome organization, but how their physical properties shape 3D chromatin architecture remains unclear. 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. Our findings define a mechanical role for enzymatic condensates that is separable yet synergistic with their catalytic function, and leaving a fine-scaled mechanical imprint on the genome.

ORGANISM(S): Saccharomyces cerevisiae

PROVIDER: GSE305782 | GEO | 2026/08/25

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Like tobacco smoking, habitual marijuana smoking causes numerous adverse pulmonary effects. However, the mechanisms of action involved, especially as compared to tobacco smoke, are still unclear. To uncover putative modes of action, this study employed a toxicogenomics approach to compare the toxicological pathways perturbed following exposure to marijuana and tobacco smoke condensate in vitro. Condensates of mainstream smoke from hand-rolled tobacco and marijuana cigarettes were similarly prepared using identical smoking conditions. Murine lung epithelial cells were exposed to low, medium and high concentrations of the smoke condensates for 6 hr. RNA was extracted immediately or after a 4-hr recovery period and hybridized to mouse whole genome microarrays. Tobacco smoke condensate (TSC) exposure was associated with changes in xenobiotic metabolism, oxidative stress, inflammation, and DNA damage response. These same pathways were also significantly affected following marijuana smoke condensate (MSC) exposure. Although the effects of the condensates were largely similar, dose-response analysis indicates that the MSC is substantially more potent than TSC. In addition, steroid biosynthesis, apoptosis, and inflammation pathways were more significantly affected following MSC exposure, whereas m-phase cell cycle pathways were more significantly affected following TSC exposure. MSC exposure also appeared to elicit more severe oxidative stress than TSC exposure, which may account for the greater cytotoxicity of MSC. This study shows that in general, MSC impacts many of the same molecular processes as TSC. However, subtle pathway differences can provide insight into the differential toxicities of the two complex mixtures. Murine epithelial lung cells were exposed to tobacco smoke condensates (0, 25, 50, 90 Î¼g/ml) or marijuana smoke condensates (0, 2.5, 5, 10 Î¼g/ml) in serum-free medium for a six hour period. Following the six-hour exposure, cells were either harvested immediately or washed with phosphate-buffered saline and incubated in fresh serum-free medium for a four hour recovery period. Total RNA was extracted from the cells and hybridized against Universal Mouse Reference RNA (Agilent Technologies Canada, Inc.) to Agilent whole mouse genome microarray slides containing 44,000 transcripts. A LOWESS normalization was applied to expression results, and statistically significant genes were identified using the R library MAANOVA. Microarray results were validated by real time RT-PCR.

Dataset Information

Ubiquitination condensates sculpt genome architecture via non-enzymatic chromatin mechanics

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets