Maji Ajoy, Ahmed Jahir A, Roy Subhankar, Chakrabarti Buddhapriya, Mitra Mithun K
Department of Physics, Indian Institute of Technology Bombay, Mumbai, India.
AKI's Poona College of Arts, Science and Commerce, Camp, Pune, India.
Biophys J. 2020 Jun 16;118(12):3041-3050. doi: 10.1016/j.bpj.2020.05.014. Epub 2020 May 20.
We propose a simple model for chromatin organization based on the interaction of the chromatin fibers with lamin proteins along the nuclear membrane. Lamin proteins are known to be a major factor that influences chromatin organization and hence gene expression in the cells. We provide a quantitative understanding of lamin-associated chromatin organization in a crowded macromolecular environment by systematically varying the heteropolymer segment distribution and the strength of the lamin-chromatin attractive interaction. Our minimal polymer model reproduces the formation of lamin-associated-domains and provides an in silico tool for quantifying domain length distributions for different distributions of heteropolymer segments. We show that a Gaussian distribution of heteropolymer segments, coupled with strong lamin-chromatin interactions, can qualitatively reproduce observed length distributions of lamin-associated-domains. Further, lamin-mediated interaction can enhance the formation of chromosome territories as well as the organization of chromatin into tightly packed heterochromatin and the loosely packed gene-rich euchromatin regions.
我们基于染色质纤维与沿核膜的核纤层蛋白之间的相互作用，提出了一个简单的染色质组织模型。已知核纤层蛋白是影响染色质组织进而影响细胞中基因表达的主要因素。通过系统地改变杂聚物片段分布和核纤层蛋白 - 染色质吸引相互作用的强度，我们对拥挤的大分子环境中与核纤层蛋白相关的染色质组织进行了定量理解。我们的最小聚合物模型再现了与核纤层蛋白相关结构域的形成，并提供了一种计算机模拟工具，用于量化不同杂聚物片段分布下的结构域长度分布。我们表明，杂聚物片段的高斯分布，再加上强烈的核纤层蛋白 - 染色质相互作用，能够定性地再现观察到的与核纤层蛋白相关结构域的长度分布。此外，核纤层蛋白介导的相互作用可以增强染色体区域的形成，以及染色质组织成紧密堆积的异染色质和松散堆积的富含基因的常染色质区域。
