期刊
NUCLEIC ACIDS RESEARCH
卷 48, 期 20, 页码 11284-11303出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkaa871
关键词
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资金
- Simons Foundation
- National Science Foundation [DMS-1462992, DMS-1816630, 1929114]
- National Institutes of Health [R37 GM32238]
- Div Of Molecular and Cellular Bioscience
- Direct For Biological Sciences [1929114] Funding Source: National Science Foundation
The revolution in understanding higher order chromosome dynamics and organization derives from treating the chromosome as a chain polymer and adapting appropriate polymer-based physical principles. Using basic principles, such as entropic fluctuations and timescales of relaxation of Rouse polymer chains, one can recapitulate the dominant features of chromatin motion observed in vivo. An emerging challenge is to relate the mechanical properties of chromatin to more nuanced organizational principles such as ubiquitous DNA loops. Toward this goal, we introduce a real-time numerical simulation model of a long chain polymer in the presence of histones and condensin, encoding physical principles of chromosome dynamics with coupled histone and condensin sources of transient loop generation. An exact experimental correlate of the model was obtained through analysis of a model-matching fluorescently labeled circular chromosome in live yeast cells. We show that experimentally observed chromosome compaction and variance in compaction are reproduced only with tandem interactions between histone and condensin, not from either individually. The hierarchical loop structures that emerge upon incorporation of histone and condensin activities significantly impact the dynamic and structural properties of chromatin. Moreover, simulations reveal that tandem condensin-histone activity is responsible for higher order chromosomal structures, including recently observed Z-loops. [GRAPHICS] .
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