期刊
BIOPHYSICAL JOURNAL
卷 115, 期 9, 页码 1644-1655出版社
CELL PRESS
DOI: 10.1016/j.bpj.2018.06.032
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资金
- Intramural Research Program of the National Institutes of Health, National Cancer Institute
- NATIONAL CANCER INSTITUTE [ZIABC010844] Funding Source: NIH RePORTER
To elucidate conformational dynamics of chromatin fibers, we compared available force-spectroscopy measurements with extensive Monte Carlo simulations of nucleosome arrays under external force. Our coarse-grained model of chromatin includes phenomenological energy terms for the DNA-histone adhesion and the internucleosome stacking interactions. We found that the Monte Carlo fiber ensembles simulated with increasing degrees of DNA unwrapping and the stacking energy 8 kT can account for the intricate force-extension response observed experimentally. Our analysis shows that at low external forces (F< 3.0 picoNewtons), the DNA ends in nucleosomes breathe by similar to 10 bp. Importantly, under these conditions, the fiber is highly dynamic, exhibiting continuous unstacking-restacking transitions, allowing accessibility of transcription factors to DNA, while maintaining a relatively compact conformation. Of note, changing the stacking interaction by a few kT, an in silico way to mimic histone modifications, is sufficient to transform an open chromatin state into a compact fiber. The fibers are mostly two-start zigzag folds with rare occurrences of three- to five-start morphologies. The internucleosome stacking is lost during the linear response regime. At the higher forces exceeding 4 picoNewtons, the nucleosome unwrapping becomes stochastic and asymmetric, with one DNA arm opened by similar to 55 bp and the other arm only by similar to 10 bp. Importantly, this asymmetric unwrapping occurs for any kind of sequence, including the symmetric ones. Our analysis brings new, to our knowledge, insights in dynamics of chromatin modulated by histone epigenetic modifications and molecular motors such as RNA polymerase.
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