3D Reconstruction of Dinoflagellate Chromosomes from Hi-C Data Challenges the Cholesteric Liquid Crystal Hypothesis

Dinoflagellates have permanently condensed chromosomes that are often described as cholesteric liquid crystals (CLCs). The CLC model proposes that DNA is organized into parallel fibers within stacked discs, such that the fiber orientation rotates between adjacent discs. Extrachromosomal loops extending from the discs are hypothesized to be more accessible and thus to contain transcriptionally active genes. Although the CLC model captures some features of dinoflagellate chromosome structure, its validity has not been rigorously tested against modern genomic data. Here, we use chromatin conformation capture (Hi-C) data to simulate 3D conformations of chromosome scaffolds for three dinoflagellate species: Fugacium kawagutii, Symbiodinium microadriaticum, and Breviolum minutum. Consensus and population-based modeling generate diverse polymer conformations with moderate orientational and nematic order. However, we find no evidence of cholesteric discs. Moreover, contact probability curves from empirical Hi-C data are inconsistent with the CLC model. Nevertheless, we show that introducing locus-specific boundaries into CLCs can produce simulated Hi-C contact maps with topologically associating domains (TADs), which are observed experimentally for these species. Finally, by mapping RNA-seq data onto our simulated conformations, we find no enrichment of transcriptional activity at the chromosome periphery. Our results challenge the long-standing CLC model and suggest that dinoflagellate chromosomes are organized into condensed structures with local but not global order that does not impede transcription. Philipp et al. model 3D chromosome conformations from Hi-C and RNA-seq data from three dinoflagellate species, challenging long-held assumptions about cholesteric liquid crystal organization and transcriptional enrichment at chromosome peripheries.