Hafner Antonina, Boettiger Alistair
Department of Developmental Biology, Stanford University, Stanford, CA, USA.
Nat Rev Genet. 2023 Jan;24(1):53-68. doi: 10.1038/s41576-022-00526-0. Epub 2022 Sep 14.
In animals, the sequences for controlling gene expression do not concentrate just at the transcription start site of genes, but are frequently thousands to millions of base pairs distal to it. The interaction of these sequences with one another and their transcription start sites is regulated by factors that shape the three-dimensional (3D) organization of the genome within the nucleus. Over the past decade, indirect tools exploiting high-throughput DNA sequencing have helped to map this 3D organization, have identified multiple key regulators of its structure and, in the process, have substantially reshaped our view of how 3D genome architecture regulates transcription. Now, new tools for high-throughput super-resolution imaging of chromatin have directly visualized the 3D chromatin organization, settling some debates left unresolved by earlier indirect methods, challenging some earlier models of regulatory specificity and creating hypotheses about the role of chromatin structure in transcriptional regulation.
在动物中，控制基因表达的序列并不只集中在基因的转录起始位点，而是常常位于其下游数千到数百万个碱基对处。这些序列彼此之间以及与它们的转录起始位点的相互作用，受到一些因素的调控，这些因素塑造了细胞核内基因组的三维（3D）结构。在过去十年中，利用高通量DNA测序的间接工具帮助绘制了这种3D结构，确定了其结构的多个关键调节因子，并且在此过程中，极大地重塑了我们对3D基因组结构如何调控转录的看法。现在，用于染色质高通量超分辨率成像的新工具已经直接可视化了3D染色质结构，解决了一些早期间接方法未解决的争议，挑战了一些早期的调控特异性模型，并提出了关于染色质结构在转录调控中作用的假设。
