Chromatin end-anchored chromosome-sized domains and promoter loops organize a transcriptionally active genome in Tetrahymena

• 成果类型: Article
• 署名作者: Hu, Tengfei; Song, Xiaoyuan; Luo, Zhengyu
• 署名单位: Chinese Academy of Sciences; University of Science & Technology of China, CAS
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2607976123
• 发表日期: 2026-07-21
• 页码: e2607976123
• 关键词: 3D genome organization; chromatin loops; telomere interactions; Micro-C; tetrahymena; hi-c; NUCLEAR REORGANIZATION; CONDENSIN COMPLEX; architecture; principles; segregation; nucleosome; yeast; ctcf

摘要

Three-dimensional (3D) genome architecture shapes gene regulation, yet the folding principles of compact unicellular genomes remain unclear. Among unicellular eukaryotes, the ciliate Tetrahymena thermophila provides a distinctive model, harboring a transcriptionally active somatic macronucleus (MAC) with a genome fragmented into gene-dense minichromosomes and a silent, intact germline micronucleus. To delineate macronuclear chromatin organization, we integrated nucleosome-resolution Micro-C, ATAC-seq, and RNA-seq across the Tetrahymena life cycle. We find that macronuclear chromosomes form chromosome-sized interaction domains rather than canonical A/B compartments or internal TAD-like hierarchical structures. Each macronuclear chromosome behaves as a telomere-bounded structural unit organized by two major features: Highly accessible telomere-capped ends form stable end-end interaction hubs, and promoter-proximal open chromatin sites anchor long-range internal promoter-centered loops whose strength correlates with transcriptional activity. During conjugation, the sexual life cycle of Tetrahymena, long-range internal loops, and promoter-promoter contacts are transiently diminished and subsequently restored in later conjugation stages, whereas chromosome end-end contacts remain relatively stable. A similar architecture is observed in the related ciliate Tetrahymena pyriformis, indicating conservation within the genus. Together, our results define a compact, end-anchored, and promoter-centric genome-folding strategy that organizes a fragmented, gene-dense, transcriptionally active genome without the canonical compartment/TAD hierarchy seen in metazoan genomes. These findings expand the known repertoire of eukaryotic 3D genome architectures and suggest that promoter-associated transcription hubs can evolve independently in divergent eukaryotic lineages.