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

Authors

Tengfei Hu, Xiaoyuan Song, Zhengyu Luo

Published in

Proceedings of the National Academy of Sciences of the United States of America. Volume 123. Issue 29. Pages e2607976123. Jul 21, 2026. Epub Jul 16, 2026.

Abstract

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.

PMID:
42461771
Bibliographic data and abstract were imported from PubMed on 17 Jul 2026.

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