Dynamics as a cause for the nanoscale organization of the genome

Chromatin ‘blobs’ were recently identified by live super-resolution imaging of labeled nucleosomes as pervasive but fleeting structural entities. However, the mechanisms leading to the formation of these blobs and their functional implications are unknown. We explore here whether causal relationships exist between parameters that characterize the chromatin blob dynamics and structure, by adapting a framework for spatio-temporal Granger-causality inference. Our analysis reveals that chromatin dynamics is a key determinant for both blob area and local density. Such causality, however, could be demonstrated only in 10–20% of the nucleus, suggesting that chromatin dynamics and structure at the nanometer scale are dominated by stochasticity. We show that the theory of active semiflexible polymers can be invoked to provide potential mechanisms leading to the organization of chromatin into blobs. Our results represent a first step toward elucidating the mechanisms that govern the dynamic and stochastic organization of chromatin in the cell nucleus.

近期，科研人员借助标记核小体的活细胞超分辨率成像技术，发现染色质团块（chromatin blobs）是一类广泛分布且转瞬即逝的结构实体。然而，此类团块的形成机制及其功能意义至今仍不明晰。本研究通过适配时空格兰杰因果推断（spatio-temporal Granger-causality inference）框架，探究表征染色质团块动力学与结构的各项参数间是否存在因果关联。分析结果显示，染色质动力学是团块面积与局部密度的关键决定因素。但此类因果关联仅能在细胞核内10%~20%的区域中被观测到，这提示纳米尺度下的染色质动力学与结构主要由随机性主导。本研究证实，可借助活性半柔性聚合物（active semiflexible polymers）理论阐释染色质组装为团块的潜在机制。本研究结果为阐明细胞核内染色质动态随机组装的调控机制迈出了第一步。