Histone H3K36me3 mediates the genomic instability of Benzo[a]pyrene in human bronchial epithelial cells
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View abstract on PubMed
Summary
This summary is machine-generated.Benzo[a]pyrene (BaP) exposure reduces key histone H3 methylations, impacting cell proliferation, DNA repair, and genomic stability. SETD2 downregulation by BaP exacerbates DNA damage, highlighting histone methylation
Area Of Science
- Epigenetics and Environmental Toxicology
- Chromatin Biology
- Carcinogenesis Research
Background
- Histone modifications are crucial for genomic stability and gene expression.
- Benzo[a]pyrene (BaP) is an environmental carcinogen with largely undefined epigenetic effects.
- The role of histone methylation in BaP toxicity requires elucidation.
Purpose Of The Study
- To investigate the impact of BaP on histone H3 lysine methylation.
- To determine the regulatory mechanisms of histone modification in BaP-induced toxicity.
- To elucidate the role of SETD2 and H3K36me3 in cellular responses to BaP.
Main Methods
- Treatment of HBE cells and in vivo models with BaP.
- Analysis of histone H3 methylation levels (H3K4me, H3K9me, H3K27me, H3K36me).
- SETD2 expression analysis, knockdown experiments, Chromatin Immunoprecipitation (ChIP)-seq, and RNA-seq.
Main Results
- BaP caused dose-dependent reductions in H3K4me, H3K9me, H3K27me, and H3K36me.
- Inhibition of H3K27me and H3K36me impaired cell proliferation; loss of H3K4me, H3K9me, H3K27me, and H3K36me increased genomic instability and delayed DNA repair.
- BaP downregulated SETD2, and SETD2 knockdown aggravated BaP-induced DNA damage.
- H3K36me3 regulates genes involved in cell survival, cancer, metabolism, and inflammation, with altered enrichment correlating with gene expression changes.
Conclusions
- Histone lysine methylation is critical for maintaining cellular homeostasis during BaP exposure.
- BaP-induced alterations in histone methylation, particularly H3K36me3 regulated by SETD2, contribute to its toxic effects.
- Understanding these epigenetic mechanisms is vital for addressing BaP-related health risks.
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