A chromosome-scale epigenetic map of the Hydra genome reveals conserved regulators of cell state
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Abstract
The epithelial and interstitial stem cells of the freshwater polyp Hydra are the best-characterized stem cell systems in any cnidarian, providing valuable insight into cell type evolution and the origin of stemness in animals. However, little is known about the transcriptional regulatory mechanisms that determine how these stem cells are maintained and how they give rise to their diverse differentiated progeny. To address such questions, a thorough understanding of transcriptional regulation in Hydra is needed. To this end, we generated extensive new resources for characterizing transcriptional regulation in Hydra , including new genome assemblies for Hydra oligactis and the AEP strain of Hydra vulgaris , an updated whole-animal single-cell RNA-seq atlas, and genome-wide maps of chromatin interactions, chromatin accessibility, sequence conservation, and histone modifications. These data revealed the existence of large kilobase-scale chromatin interaction domains in the Hydra genome that contain transcriptionally coregulated genes. We also uncovered the transcriptomic profiles of two previously molecularly uncharacterized cell types: isorhiza-type nematocytes and somatic gonad ectoderm. Finally, we identified novel candidate regulators of cell type–specific transcription, several of which have likely been conserved at least since the divergence of Hydra and the jellyfish Clytia hemisphaerica more than 400 million years ago.
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In non-bilaterian lineages such as cnidarians, available data suggest that topological domains are smaller, if they exist at all, and potentially less insulated.
“By contrast, in non-bilaterian lineages such as cnidarians, available data suggest that topological domains are smaller, if they exist at all (134), and potentially less insulated (135).”
From Topological Approaches in Animal Comparative Genomics (2026) · cites this paper as [135]
The Results section, “Hydra chromatin is organized into localized contact domains” (page unavailable), reports putative Hydra contact domains with a median size of about 176 kb and says some resemble TADs. It does not establish that domains in cnidarians generally are smaller than those in bilaterians. The separate claim about insulation is attached to citation 135, not this source. (LLM, conf=0.78)
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Cited by
Sorted by citations
Topological Approaches in Animal Comparative Genomics
Schultz, D. T., & Simakov, O. (2026) · Annual Review of Animal Biosciences · doi:10.1146/annurev-animal-030424-084541 · Cited by 1 · see citing works
Self-citation
- Authors
- Cazet, J. F., Siebert, S., Little, H. M., Bertemes, P., Primack, A. S., Ladurner, P., Achrainer, M., Fredriksen, M. T., Moreland, R. T., Singh, S., Zhang, S., Wolfsberg, T. G., Schnitzler, C. E., Baxevanis, A. D., Simakov, O., Hobmayer, B., & Juliano, C. E.
- Affiliations
- University of California, Davis (US)
- Lyell Immunopharma (United States) (US)
- Universität Innsbruck (AT)
- National Institutes of Health (US)
- University of Florida (US)
- University of Vienna (AT)
- Corresponding author
- Juliano, Celina E.
- ORCID
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2023-01-13
- Volume
- 33
- Issue
- 2
- Pages
- 283-298
- ISSN
- 1088-9051 (ISSN-L)
- 1549-5469
- PMC
- PMC10069465
- OpenAlex
- W4316036485
- Cited by
- 66
- References
- 13
- Citations by year
- 2026: 22 · 2025: 23 · 2024: 10 · 2023: 11
- Type
- posted content
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc
- Locations
- Genome Research (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc)
- Funders
- DNA Technologies
- UC Davis Genome Center
- NIH (1S10OD010786-01, HG000140)
- National Institutes of Health (R35 GM133689)
- Austrian Science Fund (FWF) and Deutsche Forschungsgemeinschaft (I4353)
- Austrian Science Fund (P30347)
- Fonds National de la Recherche Luxembourg (13569708)
- National Human Genome Research Institute
- Topics
- Physical Sciences › Earth and Planetary Sciences › Paleontology › Marine Invertebrate Physiology and Ecology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- Hydra, epigenetics, transcriptional regulation, chromatin interactions, chromatin accessibility, histone modifications, stem cells, cell states, Hydra oligactis, Hydra vulgaris, nematocytes, cell-type-specific transcription, Clytia hemisphaerica, cnidarian evolution, cell type evolution
- MeSH terms
- Animals, Cell Differentiation, Chromatin, Chromosomes, Hydra, Epigenesis, Genetic
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