摘要：SummaryHeterochromatin is a physical state of the chromatin fiber that maintains gene repression during cell development. Although evidence exists on molecular mechanisms involved in heterochromatin formation, a detailed structural mechanism of heterochromatin formation needs a better understanding. We made use of a simple Monte Carlo simulation model with explicit representation of key molecular events to observe molecular self-organization leading to heterochromatin formation. Our simulations provide a structural interpretation of several important traits of the heterochromatinization process. In particular, this study provides a depiction of how small amounts of HP1 are able to induce a highly condensed chromatin state through HP1 dimerization and bridging of sequence-remote nucleosomes. It also elucidates structural roots of a yet poorly understood phenomenon of a nondeterministic nature of heterochromatin formation and subsequent gene repression. Experimental chromatinin vivoassay provides an unbiased estimate of time scale of repressive response to a heterochromatin-triggering event.Graphical abstractDisplay OmittedHighlights•Proposed model accurately accounts for the entropic cost of chromatin condensation•Simulations rationalize the bridging hypothesis of chromatin compaction•The model explains observed non-determinism of heterochromatin formationComputational molecular modeling; Cell biology
