Two decades of advances in Tetrahymena: omics, genome architecture, epigenetic regulation, and programmed genome remodeling

Tetrahymena thermophila is one of the best-characterized unicellular eukaryotic models for investigating genome organization, chromatin biology, and epigenetic regulation. Over the past two decades, advances in genome sequencing and multi-omics have fundamentally reshaped the field, yielding increasingly comprehensive genomic resources that enable integrative analyses spanning linear genome sequences, chromatin states, and three-dimensional nuclear architecture. These studies have revealed distinct genome conformations between the transcriptionally active macronucleus (MAC) and transcriptionally silent micronucleus (MIC), including telomere-associated and promoter-centered folding in the MAC versus topologically associating domain (TAD)-like organization in the MIC. Concurrently, functional studies have elucidated epigenetic and chromatin-based mechanisms that coordinate transcription, genome stability, and nuclear differentiation, including DNA N 6 -methyladenine (6mA), chromatin remodeling, DNA repair, and small-RNA-guided programmed genome rearrangement during sexual development. In parallel, the ongoing expansion of genomic resources and experimental technologies has significantly broadened the molecular toolkit for functional and mechanistic dissection in Tetrahymena . Collectively, these advances establish Tetrahymena as a powerful and versatile model for probing genome plasticity, chromatin dynamics, epigenetic inheritance, and the evolutionary principles underlying eukaryotic genome regulation.