CDKN2A remodels lipid metabolism to prime glioblastoma for ferroptosis
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ABSTRACT:
PROVIDER: PRJNA965893 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:CDKN2A remodels lipid metabolism to prime glioblastoma for ferroptosis
| PRJNA965892 | ENA
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Project description:Epigenetic modifications contribute to lipid-related disorders by modulating the expression of key genes involved in lipid metabolism. Accumulating evidence suggests that lipid metabolism-mediated ferroptosis drives the progression of metabolic associated steatohepatitis (MASH) and liver injury. However, whether epigenetic mechanisms remodel lipid metabolism to regulate ferroptosis-induced liver damage remains unclear. Here, through pharmacological screening of epigenetics-related compounds and CRISPR-Cas9-based screening targeting epigenetic factors, we identified DOT1 Like Histone Lysine Methyltransferase (DOT1L) as a key sensitizer of hepatocytes to ferroptosis and subsequent liver injury, whereas inhibition of DOT1L reverses the phenomenon. Mechanistically, DOT1L catalyzes H3K79 methylation via its enzymatic activity, leading to transcriptional repression of phospholipid metabolism genes, including PLA2G7, ALDH3B1, and PLXCD3. These genes suppress ferroptosis by reducing the levels of phospholipids containing polyunsaturated fatty acids (PL-PUFAs). Furthermore, we demonstrated that the activity of DOT1L is negatively regulated by AMPK-mediated phosphorylation at Ser786. AMPK activation promotes DOT1L phosphorylation, which disrupts its interaction with partner proteins and impairs its recruitment to chromatin. Collectively, our findings reveal the AMPK–DOT1L–H3K79me2 axis as a novel lipid metabolic pathway that regulates ferroptosis and maintains hepatic homeostasis, offering new therapeutic insights for ferroptosis-related liver injury.
2026-09-12 | GSE343831 | GEO
Project description:Epigenetic regulation of DOT1L activity remodels lipid metabolism to alleviate ferroptosis-induced liver injury
| PRJNA1512767 | ENA
Project description:Epigenetic modifications contribute to lipid-related disorders by modulating the expression of key genes involved in lipid metabolism. Accumulating evidence suggests that lipid metabolism-mediated ferroptosis drives the progression of metabolic associated steatohepatitis (MASH) and liver injury. However, whether epigenetic mechanisms remodel lipid metabolism to regulate ferroptosis-induced liver damage remains unclear. Here, through pharmacological screening of epigenetics-related compounds and CRISPR-Cas9-based screening targeting epigenetic factors, we identified DOT1 Like Histone Lysine Methyltransferase (DOT1L) as a key sensitizer of hepatocytes to ferroptosis and subsequent liver injury, whereas inhibition of DOT1L reverses the phenomenon. Mechanistically, DOT1L catalyzes H3K79 methylation via its enzymatic activity, leading to transcriptional repression of phospholipid metabolism genes, including PLA2G7, ALDH3B1, and PLXCD3. These genes suppress ferroptosis by reducing the levels of phospholipids containing polyunsaturated fatty acids (PL-PUFAs). Furthermore, we demonstrated that the activity of DOT1L is negatively regulated by AMPK-mediated phosphorylation at Ser786. AMPK activation promotes DOT1L phosphorylation, which disrupts its interaction with partner proteins and impairs its recruitment to chromatin. Collectively, our findings reveal the AMPK–DOT1L–H3K79me2 axis as a novel lipid metabolic pathway that regulates ferroptosis and maintains hepatic homeostasis, offering new therapeutic insights for ferroptosis-related liver injury.
2026-09-12 | GSE343886 | GEO
Project description:Epigenetic modifications contribute to lipid-related disorders by modulating the expression of key genes involved in lipid metabolism. Accumulating evidence suggests that lipid metabolism-mediated ferroptosis drives the progression of metabolic associated steatohepatitis (MASH) and liver injury. However, whether epigenetic mechanisms remodel lipid metabolism to regulate ferroptosis-induced liver damage remains unclear. Here, through pharmacological screening of epigenetics-related compounds and CRISPR-Cas9-based screening targeting epigenetic factors, we identified DOT1 Like Histone Lysine Methyltransferase (DOT1L) as a key sensitizer of hepatocytes to ferroptosis and subsequent liver injury, whereas inhibition of DOT1L reverses the phenomenon. Mechanistically, DOT1L catalyzes H3K79 methylation via its enzymatic activity, leading to transcriptional repression of phospholipid metabolism genes, including PLA2G7, ALDH3B1, and PLXCD3. These genes suppress ferroptosis by reducing the levels of phospholipids containing polyunsaturated fatty acids (PL-PUFAs). Furthermore, we demonstrated that the activity of DOT1L is negatively regulated by AMPK-mediated phosphorylation at Ser786. AMPK activation promotes DOT1L phosphorylation, which disrupts its interaction with partner proteins and impairs its recruitment to chromatin. Collectively, our findings reveal the AMPK–DOT1L–H3K79me2 axis as a novel lipid metabolic pathway that regulates ferroptosis and maintains hepatic homeostasis, offering new therapeutic insights for ferroptosis-related liver injury.
2026-09-12 | GSE343979 | GEO
Project description:Epigenetic modifications contribute to lipid-related disorders by modulating the expression of key genes involved in lipid metabolism. Accumulating evidence suggests that lipid metabolism-mediated ferroptosis drives the progression of metabolic associated steatohepatitis (MASH) and liver injury. However, whether epigenetic mechanisms remodel lipid metabolism to regulate ferroptosis-induced liver damage remains unclear. Here, through pharmacological screening of epigenetics-related compounds and CRISPR-Cas9-based screening targeting epigenetic factors, we identified DOT1 Like Histone Lysine Methyltransferase (DOT1L) as a key sensitizer of hepatocytes to ferroptosis and subsequent liver injury, whereas inhibition of DOT1L reverses the phenomenon. Mechanistically, DOT1L catalyzes H3K79 methylation via its enzymatic activity, leading to transcriptional repression of phospholipid metabolism genes, including PLA2G7, ALDH3B1, and PLXCD3. These genes suppress ferroptosis by reducing the levels of phospholipids containing polyunsaturated fatty acids (PL-PUFAs). Furthermore, we demonstrated that the activity of DOT1L is negatively regulated by AMPK-mediated phosphorylation at Ser786. AMPK activation promotes DOT1L phosphorylation, which disrupts its interaction with partner proteins and impairs its recruitment to chromatin. Collectively, our findings reveal the AMPK–DOT1L–H3K79me2 axis as a novel lipid metabolic pathway that regulates ferroptosis and maintains hepatic homeostasis, offering new therapeutic insights for ferroptosis-related liver injury.
2026-09-12 | GSE343888 | GEO
Project description:Epigenetic modifications contribute to lipid-related disorders by modulating the expression of key genes involved in lipid metabolism. Accumulating evidence suggests that lipid metabolism-mediated ferroptosis drives the progression of metabolic associated steatohepatitis (MASH) and liver injury. However, whether epigenetic mechanisms remodel lipid metabolism to regulate ferroptosis-induced liver damage remains unclear. Here, through pharmacological screening of epigenetics-related compounds and CRISPR-Cas9-based screening targeting epigenetic factors, we identified DOT1 Like Histone Lysine Methyltransferase (DOT1L) as a key sensitizer of hepatocytes to ferroptosis and subsequent liver injury, whereas inhibition of DOT1L reverses the phenomenon. Mechanistically, DOT1L catalyzes H3K79 methylation via its enzymatic activity, leading to transcriptional repression of phospholipid metabolism genes, including PLA2G7, ALDH3B1, and PLXCD3. These genes suppress ferroptosis by reducing the levels of phospholipids containing polyunsaturated fatty acids (PL-PUFAs). Furthermore, we demonstrated that the activity of DOT1L is negatively regulated by AMPK-mediated phosphorylation at Ser786. AMPK activation promotes DOT1L phosphorylation, which disrupts its interaction with partner proteins and impairs its recruitment to chromatin. Collectively, our findings reveal the AMPK–DOT1L–H3K79me2 axis as a novel lipid metabolic pathway that regulates ferroptosis and maintains hepatic homeostasis, offering new therapeutic insights for ferroptosis-related liver injury.
2026-09-12 | GSE343887 | GEO
Project description:Epigenetic regulation of DOT1L activity remodels lipid metabolism to alleviate ferroptosis-induced liver injury [ChIP-seq]
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