Statistical Mechanics of Nucleosomes Constrained by Higher-Order Chromatin Structure.
Statistical Mechanics of Nucleosomes Constrained by Higher-Order Chromatin Structure.
复制标题
DOI：
10.1007/s10955-011-0214-y
复制
发表时间：
2011-07-01
影响因子：
1.6
通讯作者：
Morozov, Alexandre V.
中科院分区：
文献类型：
--
作者：
Chereji, Razvan V.;Morozov, Alexandre V.
关键词：
真核DNA被包装成染色质：由连接物DNA延伸分开的一维核小体阵列被折叠成30 nm的染色质纤维，染色质纤维进而形成更高级别的结构(Felsenfeld和Groudine in Natural 421：448,2003)。每个核小体是染色质的基本单位，有147个碱基对(BP)的DNA包裹在组蛋白八聚体周围(Richmond and Davey in Natural 423：145,2003)。为了描述染色质纤维的形成如何影响核小体定位和能量学，我们发展了一个有限大小粒子的热力学模型，该粒子具有有效的近邻相互作用和任意的DNA结合能。我们表明，基于体外或体内核小体位置的高通量地图，可以从单粒子密度分布中提取一体和两体相互作用。虽然一种忽略两体相互作用的更简单的方法(即使它们实际上存在于系统中)可以用来预测核小体位置的序列决定因素，但需要完整的理论来解开一体和两体效应。最后，我们构建了一个最小模型，在该模型中，核小体主要通过空间排斥和两体相互作用来定位，而不是内在的组蛋白-DNA序列偏好。该模型再现了在活细胞中转录区域观察到的核小体占据模式。
Eukaryotic DNA is packaged into chromatin: one-dimensional arrays of nucleosomes separated by stretches of linker DNA are folded into 30-nm chromatin fibers which in turn form higher-order structures (Felsenfeld and Groudine in Nature 421:448, 2003). Each nucleosome, the fundamental unit of chromatin, has 147 base pairs (bp) of DNA wrapped around a histone octamer (Richmond and Davey in Nature 423:145, 2003). In order to describe how chromatin fiber formation affects nucleosome positioning and energetics, we have developed a thermodynamic model of finite-size particles with effective nearest-neighbor interactions and arbitrary DNA-binding energies. We show that both one-and two-body interactions can be extracted from one-particle density profiles based on high-throughput maps of in vitro or in vivo nucleosome positions. Although a simpler approach that neglects two-body interactions (even if they are in fact present in the system) can be used to predict sequence determinants of nucleosome positions, the full theory is required to disentangle one- and two-body effects. Finally, we construct a minimal model in which nucleosomes are positioned primarily by steric exclusion and two-body interactions rather than intrinsic histone-DNA sequence preferences. The model reproduces nucleosome occupancy patterns observed over transcribed regions in living cells.
登录
查看更多内容
DOI：
10.1073/pnas.1003838107
发表时间：
2010-12-07
影响因子：
11.1
作者：
Locke, George;Tolkunov, Denis;Morozov, Alexandre V.
通讯作者：
Morozov, Alexandre V.
影响因子：
5.6
作者：
Lowary, PT;Widom, J
通讯作者：
Widom, J
影响因子：
64.8
作者：
Felsenfeld, G;Groudine, M
通讯作者：
Groudine, M
影响因子：
4.3
作者：
Moebius, Wolfram;Gerland, Ulrich
通讯作者：
Gerland, Ulrich
影响因子：
5.6
作者：
Thåström, A;Lowary, PT;Widom, J
通讯作者：
Widom, J