Scholarlink

<p>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 <i>cytochrome P450 1&#xa0;A</i> (<i>CYP1A</i>) gene in wild <i>Fundulus heteroclitus</i> that have adapted to chronic, extreme PAH pollution. In wild-type fish, <i>CYP1A</i> is highly induced by PAH. In PAH-tolerant fish, <i>CYP1A</i> 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 <i>CYP1A</i> inducibility, indicating a non-genetic effect. We observed epigenetic control of this reversible memory of generational PAH stress in F<sub>1</sub> PAH-tolerant embryos. We detected a bivalent domain in the <i>CYP1A</i> 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 <i>CYP1A</i> long after exposure cessation, which is consistent with defective <i>CYP1A</i> 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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

An epigenetic memory at the CYP1A gene in cancer-resistant, pollution-adapted killifish

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年1月24日

查看全文
  • Samantha Carrothers,
  • Rafael Trevisan,
  • Nishad Jayasundara,
  • Nicole Pelletier,
  • Emma Weeks,
  • Joel N. Meyer,
  • Richard Di Giulio,
  • Caren Weinhouse

摘要

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.