An epigenetic memory at the CYP1A gene in cancer-resistant, pollution-adapted killifish
Abstract Human exposure to polycyclic aromatic hydrocarbons (PAH) is a significant public health problem that will worsen with a warming climate and increased large-scale wildfires. Here, we characterize an epigenetic memory at the cytochrome P450 1 A (CYP1A) gene in wild Fundulus heteroclitus that...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-024-82740-w |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832585872986341376 |
|---|---|
| author | Samantha Carrothers Rafael Trevisan Nishad Jayasundara Nicole Pelletier Emma Weeks Joel N. Meyer Richard Di Giulio Caren Weinhouse |
| author_facet | Samantha Carrothers Rafael Trevisan Nishad Jayasundara Nicole Pelletier Emma Weeks Joel N. Meyer Richard Di Giulio Caren Weinhouse |
| author_sort | Samantha Carrothers |
| collection | DOAJ |
| description | Abstract Human exposure to polycyclic aromatic hydrocarbons (PAH) is a significant public health problem that will worsen with a warming climate and increased large-scale wildfires. Here, we characterize an epigenetic memory at the cytochrome P450 1 A (CYP1A) gene in wild Fundulus heteroclitus that have adapted to chronic, extreme PAH pollution. In wild-type fish, CYP1A is highly induced by PAH. In PAH-tolerant fish, CYP1A induction is blunted. Since CYP1A metabolically activates PAH, this memory protects these fish from PAH-mediated cancer. However, PAH-tolerant fish reared in clean water recover CYP1A inducibility, indicating a non-genetic effect. We observed epigenetic control of this reversible memory of generational PAH stress in F1 PAH-tolerant embryos. We detected a bivalent domain in the CYP1A promoter enhancer comprising both activating and repressive histone post-translational modifications. Activating modifications, relative to repressive ones, showed greater increases in response to PAH in sensitive embryos, relative to tolerant, consistent with greater gene activation. PAH-tolerant adult fish showed persistent induction of CYP1A long after exposure cessation, which is consistent with defective CYP1A shutoff. These results indicate that PAH-tolerant fish have epigenetic protection against PAH-induced cancer in early life that degrades in response to continuous gene activation. |
| format | Article |
| id | doaj-art-c491b03407f34215a5ebc0d21aab9956 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-c491b03407f34215a5ebc0d21aab99562025-01-26T12:25:05ZengNature PortfolioScientific Reports2045-23222025-01-0115111610.1038/s41598-024-82740-wAn epigenetic memory at the CYP1A gene in cancer-resistant, pollution-adapted killifishSamantha Carrothers0Rafael Trevisan1Nishad Jayasundara2Nicole Pelletier3Emma Weeks4Joel N. Meyer5Richard Di Giulio6Caren Weinhouse7Oregon Institute of Occupational Health Sciences, Oregon Health and Science UniversityNicholas School of the Environment, Duke UniversityNicholas School of the Environment, Duke UniversityOregon Institute of Occupational Health Sciences, Oregon Health and Science UniversityOregon Institute of Occupational Health Sciences, Oregon Health and Science UniversityNicholas School of the Environment, Duke UniversityNicholas School of the Environment, Duke UniversityOregon Institute of Occupational Health Sciences, Oregon Health and Science UniversityAbstract Human exposure to polycyclic aromatic hydrocarbons (PAH) is a significant public health problem that will worsen with a warming climate and increased large-scale wildfires. Here, we characterize an epigenetic memory at the cytochrome P450 1 A (CYP1A) gene in wild Fundulus heteroclitus that have adapted to chronic, extreme PAH pollution. In wild-type fish, CYP1A is highly induced by PAH. In PAH-tolerant fish, CYP1A induction is blunted. Since CYP1A metabolically activates PAH, this memory protects these fish from PAH-mediated cancer. However, PAH-tolerant fish reared in clean water recover CYP1A inducibility, indicating a non-genetic effect. We observed epigenetic control of this reversible memory of generational PAH stress in F1 PAH-tolerant embryos. We detected a bivalent domain in the CYP1A promoter enhancer comprising both activating and repressive histone post-translational modifications. Activating modifications, relative to repressive ones, showed greater increases in response to PAH in sensitive embryos, relative to tolerant, consistent with greater gene activation. PAH-tolerant adult fish showed persistent induction of CYP1A long after exposure cessation, which is consistent with defective CYP1A shutoff. These results indicate that PAH-tolerant fish have epigenetic protection against PAH-induced cancer in early life that degrades in response to continuous gene activation.https://doi.org/10.1038/s41598-024-82740-wEpigeneticsPolycyclic aromatic hydrocarbonsEnvironmental plasticityFundulus heteroclitus |
| spellingShingle | Samantha Carrothers Rafael Trevisan Nishad Jayasundara Nicole Pelletier Emma Weeks Joel N. Meyer Richard Di Giulio Caren Weinhouse An epigenetic memory at the CYP1A gene in cancer-resistant, pollution-adapted killifish Scientific Reports Epigenetics Polycyclic aromatic hydrocarbons Environmental plasticity Fundulus heteroclitus |
| title | An epigenetic memory at the CYP1A gene in cancer-resistant, pollution-adapted killifish |
| title_full | An epigenetic memory at the CYP1A gene in cancer-resistant, pollution-adapted killifish |
| title_fullStr | An epigenetic memory at the CYP1A gene in cancer-resistant, pollution-adapted killifish |
| title_full_unstemmed | An epigenetic memory at the CYP1A gene in cancer-resistant, pollution-adapted killifish |
| title_short | An epigenetic memory at the CYP1A gene in cancer-resistant, pollution-adapted killifish |
| title_sort | epigenetic memory at the cyp1a gene in cancer resistant pollution adapted killifish |
| topic | Epigenetics Polycyclic aromatic hydrocarbons Environmental plasticity Fundulus heteroclitus |
| url | https://doi.org/10.1038/s41598-024-82740-w |
| work_keys_str_mv | AT samanthacarrothers anepigeneticmemoryatthecyp1ageneincancerresistantpollutionadaptedkillifish AT rafaeltrevisan anepigeneticmemoryatthecyp1ageneincancerresistantpollutionadaptedkillifish AT nishadjayasundara anepigeneticmemoryatthecyp1ageneincancerresistantpollutionadaptedkillifish AT nicolepelletier anepigeneticmemoryatthecyp1ageneincancerresistantpollutionadaptedkillifish AT emmaweeks anepigeneticmemoryatthecyp1ageneincancerresistantpollutionadaptedkillifish AT joelnmeyer anepigeneticmemoryatthecyp1ageneincancerresistantpollutionadaptedkillifish AT richarddigiulio anepigeneticmemoryatthecyp1ageneincancerresistantpollutionadaptedkillifish AT carenweinhouse anepigeneticmemoryatthecyp1ageneincancerresistantpollutionadaptedkillifish AT samanthacarrothers epigeneticmemoryatthecyp1ageneincancerresistantpollutionadaptedkillifish AT rafaeltrevisan epigeneticmemoryatthecyp1ageneincancerresistantpollutionadaptedkillifish AT nishadjayasundara epigeneticmemoryatthecyp1ageneincancerresistantpollutionadaptedkillifish AT nicolepelletier epigeneticmemoryatthecyp1ageneincancerresistantpollutionadaptedkillifish AT emmaweeks epigeneticmemoryatthecyp1ageneincancerresistantpollutionadaptedkillifish AT joelnmeyer epigeneticmemoryatthecyp1ageneincancerresistantpollutionadaptedkillifish AT richarddigiulio epigeneticmemoryatthecyp1ageneincancerresistantpollutionadaptedkillifish AT carenweinhouse epigeneticmemoryatthecyp1ageneincancerresistantpollutionadaptedkillifish |