Laboratory of Genome Architecture and Dynamics, The Rockefeller University, 1230 York Ave., Box 176, New York, NY 10065, USA; David Rockefeller Graduate Program in Bioscience, The Rockefeller University, 1230 York Ave., New York, NY 10065, USA.
Laboratory of Genome Architecture and Dynamics, The Rockefeller University, 1230 York Ave., Box 176, New York, NY 10065, USA.
Curr Opin Cell Biol. 2023 Oct;84:102211. doi: 10.1016/j.ceb.2023.102211. Epub 2023 Aug 7.
The last two decades of work on chromosome conformation in eukaryotic nuclei have revealed a complex and highly regulated hierarchy of architectural features, from self-associating domains and compartmental interactions to locus-specific loops. Recent findings have shown that these structures are dynamic and heterogeneous, with emerging insights into the factors that shape them and implications for the control of transcription and other nuclear processes. Here, we review the latest advances in the DNA sequencing- and microscopy-based technologies for probing these features in space and time (4D) and discuss how they have been combined with complementary approaches such as genetic perturbations, protein and RNA measurements, and modeling to gain mechanistic insights about genome regulation across space and time.
过去二十年在真核细胞核内的染色体构象方面的研究揭示了一个复杂且高度调控的结构层次,从自组装结构域和隔室相互作用到特定基因座的环。最近的发现表明这些结构是动态和异质的,对于形成这些结构的因素以及对转录和其他核过程的控制的影响有了新的认识。在这里,我们回顾了基于 DNA 测序和显微镜的最新技术在空间和时间(4D)上探测这些结构的最新进展,并讨论了它们如何与遗传扰动、蛋白质和 RNA 测量以及建模等互补方法相结合,以获得关于基因组在空间和时间上调控的机制见解。