Journal
ISCIENCE
Volume 25, Issue 7, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.isci.2022.104590
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Funding
- National Institutes of Health [R01GM132299, R01GM118653]
- UNC Eshelman Institute for Innovation [RX03512109, RX03712111]
- University of North Carolina, Chapel Hill
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This study used a simulation model to observe molecular self-organization leading to heterochromatin formation and provided a structural interpretation of important traits of the heterochromatinization process. The study also elucidated the time scale of repressive response to a heterochromatin-triggering event.
Heterochromatin is a physical state of the chromatin fiber that maintains gene repression during cell development. Although evidence exists on molecular mech-anisms involved in heterochromatin formation, a detailed structural mechanism of heterochromatin formation needs a better understanding. We made use of a sim-ple Monte Carlo simulation model with explicit representation of key molecular events to observe molecular self-organization leading to heterochromatin forma-tion. 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 chro-matin state through HP1 dimerization and bridging of sequence-remote nucleo-somes. It also elucidates structural roots of a yet poorly understood phenomenon of a nondeterministic nature of heterochromatin formation and subsequent gene repression. Experimental chromatin in vivo assay provides an unbiased estimate of time scale of repressive response to a heterochromatin-triggering event.
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