Polymer Models of Meiotic and Mitotic Chromosomes

Polymers tied together by constraints exhibit an internal pressure; this idea is used to analyze physical properties of the bottle-brush–like chromosomes of meiotic prophase that consist of polymer-like flexible chromatin loops, attached to a central axis. Using a minimal number of experimental parameters, semiquantitative predictions are made for the bending rigidity, radius, and axial tension of such brushes, and the repulsion acting between brushes whose bristles are forced to overlap. The retraction of lampbrush loops when the nascent transcripts are stripped away, the oval shape of diplotene bivalents between chiasmata, and the rigidity of pachytene chromosomes are all manifestations of chromatin pressure. This two-phase (chromatin plus buffer) picture that suffices for meiotic chromosomes has to be supplemented by a third constituent, a chromatin glue to understand mitotic chromosomes, and explain how condensation can drive the resolution of entanglements. This process resembles a thermal annealing in that a parameter (the affinity of the glue for chromatin and/or the affinity of the chromatin for buffer) has to be tuned to achieve optimal results. Mechanical measurements to characterize this protein–chromatin matrix are proposed. Finally, the propensity for even slightly chemically dissimilar polymers to phase separate (cluster like with like) can explain the apparent segregation of the chromatin into A+T- and G+C-rich regions revealed by chromosome banding.

受约束相互连接的聚合物会展现出内压；这一思路被用于分析减数分裂前期（meiotic prophase）瓶刷状（bottle-brush-like）染色体的物理性质，该类染色体由类聚合物柔性染色质环（chromatin loops）构成，并附着于中心轴上。仅通过少量实验参数，即可对这类瓶刷结构的弯曲刚度、半径与轴向张力，以及刷毛被迫重叠的瓶刷之间的排斥作用给出半定量预测。当新生转录本（nascent transcripts）被剥离时灯刷环（lampbrush loops）的收缩、交叉（chiasmata）间双线期二价体（diplotene bivalents）的椭圆形形态，以及粗线期染色体（pachytene chromosomes）的刚度，均为染色质内压的具体表现。这一适用于减数分裂染色体的两相（染色质+缓冲液）模型，需补充第三种组分——染色质胶（chromatin glue），方能解释有丝分裂染色体（mitotic chromosomes）的相关现象，并阐明染色体凝缩如何驱动缠结的解除。该过程类似热退火（thermal annealing）：需调控某一参数（染色质胶对染色质的亲和力，或染色质对缓冲液的亲和力）以获得最优效果。本研究提出了用于表征该蛋白质-染色质基质的力学测量方案。最后，即便化学性质仅有细微差异的聚合物也存在相分离（phase separation）（同类聚集）的倾向，这一特性可解释染色体显带（chromosome banding）技术所揭示的染色质分离为A-T富集区与G-C富集区的现象。