Polymer models of mitotic and interphase chromosomes

项目总结 长期以来，染色体的空间组织一直与它们的聚合体有关 被认为对它们的生物功能很重要，包括控制 基因组元素之间的相互作用，遗传信息的维护，以及 染色体的紧凑和安全地转移到细胞后代。染色体 构象捕捉技术，特别是Hi-C和显微镜技术提供了一种 空间染色体组织的全貌和揭示的新特征 和染色体折叠的元素。聚合物模型和新的微扰数据 在过去两年中产生的，导致了对新分子的鉴定 大规模基因组组织背后的机制。两大机制 在这个项目的过程中发现的东西推动了这一领域的发展。第一，是主动的 (依赖于ATP的)通过维持染色体结构的环挤出过程 (SMC)复合体。这一普遍的机制构成了 有丝分裂中的间期、染色体紧凑和分离。第二，是不是 亲和力介导的异染色区之间的相互作用 基因组在整个核的规模上的区隔。建议 该项目旨在研究环挤出的机制，了解基因是如何 表达并影响排出，从而重新折叠染色体，最后，发育 用聚合物模拟和现场相结合的方法检测活体环状挤出 细胞成像。这些目标加在一起，可以显示环路是否以及如何挤出 在体内工作，为了解它的功能作用和分子开辟了途径 机械装置。

PROJECT SUMMARY The spatial organization of chromosomes has long been connected to their polymeric nature and is believed to be important for their biological functions, including the control of interactions between genomic elements, the maintenance of genetic information, and the compaction and safe transfer of chromosomes to cellular progeny. Chromosome conformation capture techniques, particularly Hi-C, and microscopy have provided a comprehensive picture of spatial chromosome organization and revealed new features and elements of chromosome folding. Polymer models and new perturbation data generated in the last two years have led to the identification of novel molecular mechanisms behind large-scale genome organization. Two major mechanisms discovered in the course of this project have moved the field forward. First, is the active (ATP-dependent) process of loop extrusion by Structural Maintenance of Chromosomes (SMC) complexes. This universal mechanism underlies formation of domains in the interphase, and chromosome compaction and segregation in mitosis. Second, is the affinity-mediated interactions between heterochromatic regions that drive spatial compartmentalization of the genome at the scale of the whole nucleus. Proposed project aimed at examining mechanisms of loop extrusion, understanding how gene expression and affect extrusion and hence refold chromosomes, and, finally, developing methods to detect loop extrusion in vivo by combination of polymer simulations and live cell imaging. Together, these aims could show whether and how loop extrusion operates in vivo, opening avenues to understand it functional roles and molecular mechanisms.