Physics Department, Emory University, Atlanta, GA 30322, USA.
Department of Chemistry and Biochemistry, Florida International University, Miami, FL 33199, USA.
Nucleic Acids Res. 2021 Nov 18;49(20):11550-11559. doi: 10.1093/nar/gkab946.
Protein-mediated DNA looping is fundamental to gene regulation and such loops occur stochastically in purified systems. Additional proteins increase the probability of looping, but these probabilities maintain a broad distribution. For example, the probability of lac repressor-mediated looping in individual molecules ranged 0-100%, and individual molecules exhibited representative behavior only in observations lasting an hour or more. Titrating with HU protein progressively compacted the DNA without narrowing the 0-100% distribution. Increased negative supercoiling produced an ensemble of molecules in which all individual molecules more closely resembled the average. Furthermore, in only 12 min of observation, well within the doubling time of the bacterium, most molecules exhibited the looping probability of the ensemble. DNA supercoiling, an inherent feature of all genomes, appears to impose time-constrained, emergent behavior on otherwise random molecular activity.
蛋白质介导的 DNA 环化是基因调控的基础，这种环化在纯化系统中随机发生。额外的蛋白质会增加环化的概率，但这些概率保持广泛的分布。例如，在单个分子中，乳糖阻遏物介导的环化概率在 0-100%之间变化，并且只有在持续一小时或更长时间的观察中，单个分子才表现出代表性行为。用 HU 蛋白滴定逐渐使 DNA 紧凑化，而不会缩小 0-100%的分布。增加负超螺旋产生了一个分子集合，其中所有单个分子更接近平均值。此外，在仅 12 分钟的观察时间内，远在细菌的倍增时间内，大多数分子表现出了集合的环化概率。DNA 超螺旋化是所有基因组的固有特征，它似乎对原本随机的分子活动施加了时间约束的涌现行为。
