纽约大学格罗斯曼医学院Evgeny Nudler小组宣布他们的研究开发出了活性和沉默大肠杆菌基因组的基本三维组织。相关论文发表在2025年8月13日出版的《自然》杂志上。

在这里，该课题组开发了一种增强的Micro-C染色体构象捕获，达到10个碱基对（bp）的分辨率。这种超高分辨率的分析揭示了大肠杆菌类核的基本空间结构，包括染色体发夹结构域（CHINs）和染色体发夹结构域（CHIDs）。这些结构由组蛋白样蛋白H-NS和StpA组织，在抑制水平转移基因中起关键作用。破坏H-NS会导致3D基因组的剧烈重组，减少CHINs和CHIDs，而去除H-NS和StpA会导致它们完全解体，增加水平转移基因的转录并延迟生长。netropsin也有类似的作用，它与H-NS和StpA竞争富含AT的DNA结合。CHIN之间的相互作用进一步将基因组组织成孤立的环，潜在地隔离了活性操纵子。他们的Micro-C分析显示，所有活性转录基因以转录依赖的方式形成不同的操纵子大小的染色体相互作用结构域（OPCIDs）。这些结构在Micro-C地图上显示为方形图案，反映了整个转录区域的连续接触。这项工作揭示了大肠杆菌类核的基本结构要素，突出了它们与核相关蛋白和转录机制的联系。

据悉，揭示基因组是如何在空间上组织的，以及它们的三维（3D）结构是如何驱动细胞功能的，仍然是生物学中的一个主要挑战。在细菌中，基因组DNA被压缩成一种高度有序的浓缩状态，称为核。尽管近几十年来在表征细菌三维基因组结构方面取得了进展，但由于Hi-C9等方法的低分辨率接触图谱，类核的精细结构和功能组织仍然很薄弱。

附：英文原文

Title: Elementary 3D organization of active and silenced E. coli genome

Author: Gavrilov, Alexey A., Shamovsky, Ilya, Zhegalova, Irina, Proshkin, Sergey, Shamovsky, Yosef, Evko, Grigory, Epshtein, Vitaly, Rasouly, Aviram, Blavatnik, Anna, Lahiri, Sudipta, Rothenberg, Eli, Razin, Sergey V., Nudler, Evgeny

Issue&Volume: 2025-08-13

Abstract: Unravelling how genomes are spatially organized and how their three-dimensional (3D) architecture drives cellular functions remains a major challenge in biology1,2. In bacteria, genomic DNA is compacted into a highly ordered, condensed state called nucleoid3,4,5. Despite progress in characterizing bacterial 3D genome architecture over recent decades6,7,8, the fine structure and functional organization of the nucleoid remain elusive due to low-resolution contact maps from methods such as Hi-C9,10,11. Here we developed an enhanced Micro-C chromosome conformation capture, achieving 10-base pair (bp) resolution. This ultra-high-resolution analysis reveals elemental spatial structures in the Escherichia coli nucleoid, including chromosomal hairpins (CHINs) and chromosomal hairpin domains (CHIDs). These structures, organized by histone-like proteins H-NS and StpA, have key roles in repressing horizontally transferred genes. Disruption of H-NS causes drastic reorganization of the 3D genome, decreasing CHINs and CHIDs, whereas removing both H-NS and StpA results in their complete disassembly, increased transcription of horizontally transferred genes and delayed growth. Similar effects are observed with netropsin, which competes with H-NS and StpA for AT-rich DNA binding. Interactions between CHINs further organize the genome into isolated loops, potentially insulating active operons. Our Micro-C analysis reveals that all actively transcribed genes form distinct operon-sized chromosomal interaction domains (OPCIDs) in a transcription-dependent manner. These structures appear as square patterns on Micro-C maps, reflecting continuous contacts throughout transcribed regions. This work unveils the fundamental structural elements of the E. coli nucleoid, highlighting their connection to nucleoid-associated proteins and transcription machinery.

DOI: 10.1038/s41586-025-09396-y

Source: https://www.nature.com/articles/s41586-025-09396-y