Brückner David B, Chen Hongtao, Barinov Lev, Zoller Benjamin, Gregor Thomas
Institute of Science and Technology, Am Campus 1, 3400 Klosterneuburg, Austria.
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.
bioRxiv. 2023 Feb 13:2023.01.18.524527. doi: 10.1101/2023.01.18.524527.
Chromosomes in the eukaryotic nucleus are highly compacted. However, for many functional processes, including transcription initiation, the 3D pair-wise motion of distal chromosomal elements, such as enhancers and promoters, is essential and necessitates dynamic fluidity. Therefore, the interplay of chromosome organization and dynamics is crucial for gene regulation. Here, we use a live imaging assay to simultaneously measure the positions of pairs of enhancers and promoters and their transcriptional output in the developing fly embryo while systematically varying the genomic separation between these two DNA loci. Our analysis reveals a combination of a compact globular organization and fast subdiffusive dynamics. These combined features cause an anomalous scaling of polymer relaxation times with genomic separation and lead to long-ranged correlations compared to existing polymer models. This scaling implies that encounter times of DNA loci are much less dependent on genomic separation than predicted by existing polymer models, with potentially significant consequences for eukaryotic gene expression.
真核细胞核中的染色体高度压缩。然而，对于许多功能过程，包括转录起始，远端染色体元件（如增强子和启动子）的三维成对运动至关重要，且需要动态流动性。因此，染色体组织与动态性之间的相互作用对于基因调控至关重要。在这里，我们使用实时成像分析方法，在发育中的果蝇胚胎中同时测量增强子和启动子对的位置及其转录输出，同时系统地改变这两个DNA位点之间的基因组间隔。我们的分析揭示了紧密球状组织和快速亚扩散动力学的结合。这些综合特征导致聚合物弛豫时间与基因组间隔呈现异常标度，并与现有的聚合物模型相比产生长程相关性。这种标度意味着DNA位点的相遇时间比现有聚合物模型预测的更不依赖于基因组间隔，这可能对真核基因表达产生重大影响。
