A Thermodynamic Framework for Chromatin Structure and Function

Abstract Background: Modern biology lacks a small-axiom, parameter-free framework toexplain why genome architecture, gene regulation, mutation repair, and organ-ismal diversity exhibit consistent ceilings. Information-Pressure Theory (IPT)proposes a fundamental entropy-capacity inequality, originally derived in physics,that can unify these phenomena. Results: We validate eighteen empirically-observed biological limits (e.g. TADsizes, enhancer ranges, coding fractions, transcription bubble lengths, polymerasespeeds, burst timings, overstretch forces, methylation thresholds, nucleosomebreathing times, mutation hotspots, mid-blastula transitions, immune-repertoirediversity) against IPT’s axiomatic bounds, using Hi-C, single-molecule FRET,DNA-combing, synthetic genome, and immune-sequencing datasets. Seventeendata-backed ceilings agree with IPT within ±10%. Five conceptual insights—such as “junk DNA” as entropy sinks, promoter logic as Boolean flux algebra,mutation hotspots as torsional-pressure functionals, entropy clocks for devel-opmental timing, and entropy-overflow ceilings linking synthetic genomes toimmune repertoires—emerge directly. Sensitivity analysis confirms robustness toparameter variation. Conclusions: These results position IPT as a unifying thermodynamic frame-work from nucleosome mechanics to organismal diversity, and suggest concrete,falsifiable assays in genomics, synthetic biology, oncology, and immunology.