当前位置: X-MOL 学术Biophys. J. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Heterogeneous interactions and polymer entropy decide organization and dynamics of chromatin domains
Biophysical Journal ( IF 3.2 ) Pub Date : 2022-06-06 , DOI: 10.1016/j.bpj.2022.06.008
Kiran Kumari 1 , J Ravi Prakash 2 , Ranjith Padinhateeri 3
Affiliation  

Chromatin is known to be organized into multiple domains of varying sizes and compaction. While these domains are often imagined as static structures, they are highly dynamic and show cell-to-cell variability. Since processes such as gene regulation and DNA replication occur in the context of these domains, it is important to understand their organization, fluctuation, and dynamics. To simulate chromatin domains, one requires knowledge of interaction strengths among chromatin segments. Here, we derive interaction-strength parameters from experimentally known contact maps and use them to predict chromatin organization and dynamics. Taking two domains on the human chromosome as examples, we investigate its three-dimensional organization, size/shape fluctuations, and dynamics of different segments within a domain, accounting for hydrodynamic effects. Considering different cell types, we quantify changes in interaction strengths and chromatin shape fluctuations in different epigenetic states. Perturbing the interaction strengths systematically, we further investigate how epigenetic-like changes can alter the spatio-temporal nature of the domains. Our results show that heterogeneous weak interactions are crucial in determining the organization of the domains. Computing effective stiffness and relaxation times, we investigate how perturbations in interactions affect the solid- and liquid-like nature of chromatin domains. Quantifying dynamics of chromatin segments within a domain, we show how the competition between polymer entropy and interaction energy influence the timescales of loop formation and maintenance of stable loops.



中文翻译:

异质相互作用和聚合物熵决定染色质域的组织和动态

已知染色质被组织成不同大小和压缩程度的多个域。虽然这些域通常被认为是静态结构,但它们是高度动态的,并且显示出细胞间的变异性。由于基因调控和 DNA 复制等过程发生在这些领域的背景下,因此了解它们的组织、波动和动态非常重要。为了模拟染色质域,需要了解染色质片段之间的相互作用强度。在这里,我们从实验上已知的接触图导出相互作用强度参数,并用它们来预测染色质组织和动力学。以人类染色体上的两个域为例,我们研究了其三维组织、大小/形状波动以及域内不同片段的动态,从而解释了流体动力学效应。考虑到不同的细胞类型,我们量化了不同表观遗传状态下相互作用强度的变化和染色质形状波动。系统地扰动相互作用强度,我们进一步研究表观遗传变化如何改变域的时空性质。我们的结果表明,异质弱相互作用对于确定域的组织至关重要。通过计算有效刚度和松弛时间,我们研究了相互作用中的扰动如何影响染色质域的固体和液体性质。通过量化域内染色质片段的动态,我们展示了聚合物熵和相互作用能之间的竞争如何影响环形成和稳定环维持的时间尺度。

更新日期:2022-06-06
down
wechat
bug