#20 · Genomics

Perturbation and prediction link regulatory elements and chromatin to transcript output

The common thread across these four preprints is connecting regulatory sequence and chromatin state to transcriptional output through perturbation, measurement and prediction. Swap-seq couples pooled twin prime editing with flow sorting to delete endogenous sequences and quantify enhancer, silencer and insulator effects. A nanopore study in yeast ISW1/CHD1 mutants profiles chromatin fibers and RNA together, with EpiFLAIR linking single-molecule nucleosome states to isoform-level fidelity. Engineered regulatory states in RPE-1 cells, built with CRISPRa and multiome Perturb-seq, connect chromatin opening at AMD GWAS variants to emergent regulatory outcomes. Borzoi-SE detects cell-type-resolved super-enhancers from DNA sequence alone and prioritizes causal non-coding variants. What is new is resolution: element function, nucleosome states and isoform output are assessed at single-element or single-molecule scale, tying perturbation directly to transcript-level outcomes.