IDH1 regulates human erythropoiesis by eliciting chromatin state reprogramming
Isocitrate dehydrogenase 1 (IDH1) is the key enzyme that can modulate cellular metabolism, epigenetic modification, and redox homeostasis. Gain-of-function mutations and decreased expression of IDH1 have been demonstrated to be associated with pathogenesis of various myeloid malignancies characteriz...
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eLife Sciences Publications Ltd
2025-04-01
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| Online Access: | https://elifesciences.org/articles/100406 |
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| author | Mengjia Li Hengchao Zhang Xiuyun Wu Mengqi Yu Qianqian Yang Lei Sun Wei Li Zhongxing Jiang Fumin Xue Ting Wang Xiuli An Lixiang Chen |
| author_facet | Mengjia Li Hengchao Zhang Xiuyun Wu Mengqi Yu Qianqian Yang Lei Sun Wei Li Zhongxing Jiang Fumin Xue Ting Wang Xiuli An Lixiang Chen |
| author_sort | Mengjia Li |
| collection | DOAJ |
| description | Isocitrate dehydrogenase 1 (IDH1) is the key enzyme that can modulate cellular metabolism, epigenetic modification, and redox homeostasis. Gain-of-function mutations and decreased expression of IDH1 have been demonstrated to be associated with pathogenesis of various myeloid malignancies characterized by ineffective erythropoiesis, such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). However, the function and mechanism of IDH1 in human erythropoiesis still remains unclear. Here, utilizing the human erythropoiesis system, we present an evidence of IDH1-mediated chromatin state reprogramming besides its well-characterized metabolism effects. We found that knockdown IDH1 induced chromatin reorganization and subsequently led to abnormalities biological events in erythroid precursors, which could not be rescued by addition of reactive oxygen species (ROS) scavengers or supplementation of α-ketoglutarate (α-KG).We further revealed that knockdown IDH1 induces genome-wide changes in distribution and intensity of multiple histone marks, among which H3K79me3 was identified as a critical factor in chromatin state reprogramming. Integrated analysis of ChIP-seq, ATAC-seq, and RNA-seq recognized that SIRT1 was the key gene affected by IDH1 deficiency. Thus, our current work provided novel insights for further clarifying fundamental biological function of IDH1 which has substantial implications for an in-depth understanding of pathogenesis of diseases with IDH1 dysfunction and accordingly development of therapeutic strategies. |
| format | Article |
| id | doaj-art-cab91ee5cec145c28e9308742ad5d383 |
| institution | DOAJ |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-cab91ee5cec145c28e9308742ad5d3832025-08-20T02:40:14ZengeLife Sciences Publications LtdeLife2050-084X2025-04-011310.7554/eLife.100406IDH1 regulates human erythropoiesis by eliciting chromatin state reprogrammingMengjia Li0https://orcid.org/0009-0002-1170-4946Hengchao Zhang1https://orcid.org/0000-0001-9873-9986Xiuyun Wu2https://orcid.org/0000-0003-3607-3191Mengqi Yu3https://orcid.org/0009-0007-5949-6978Qianqian Yang4https://orcid.org/0009-0008-0195-833XLei Sun5https://orcid.org/0009-0000-8697-7514Wei Li6https://orcid.org/0000-0001-5550-508XZhongxing Jiang7https://orcid.org/0000-0002-0277-4574Fumin Xue8https://orcid.org/0000-0002-6199-0592Ting Wang9https://orcid.org/0009-0002-1203-303XXiuli An10https://orcid.org/0000-0002-3582-9404Lixiang Chen11https://orcid.org/0000-0001-7785-2496State Key Laboratory of Metabolic Dysregulation and Prevention and Treatment of Esophageal Cancer; School of Life Sciences, Zhengzhou University, Zhengzhou, China; Department of Hematology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaState Key Laboratory of Metabolic Dysregulation and Prevention and Treatment of Esophageal Cancer; School of Life Sciences, Zhengzhou University, Zhengzhou, ChinaState Key Laboratory of Metabolic Dysregulation and Prevention and Treatment of Esophageal Cancer; School of Life Sciences, Zhengzhou University, Zhengzhou, ChinaState Key Laboratory of Metabolic Dysregulation and Prevention and Treatment of Esophageal Cancer; School of Life Sciences, Zhengzhou University, Zhengzhou, ChinaState Key Laboratory of Metabolic Dysregulation and Prevention and Treatment of Esophageal Cancer; School of Life Sciences, Zhengzhou University, Zhengzhou, ChinaState Key Laboratory of Metabolic Dysregulation and Prevention and Treatment of Esophageal Cancer; School of Life Sciences, Zhengzhou University, Zhengzhou, ChinaDepartment of Hematology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Hematology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Gastroenterology, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, ChinaState Key Laboratory of Metabolic Dysregulation and Prevention and Treatment of Esophageal Cancer; School of Life Sciences, Zhengzhou University, Zhengzhou, ChinaLaboratory of Membrane Biology, New York Blood Center, New York, United StatesState Key Laboratory of Metabolic Dysregulation and Prevention and Treatment of Esophageal Cancer; School of Life Sciences, Zhengzhou University, Zhengzhou, ChinaIsocitrate dehydrogenase 1 (IDH1) is the key enzyme that can modulate cellular metabolism, epigenetic modification, and redox homeostasis. Gain-of-function mutations and decreased expression of IDH1 have been demonstrated to be associated with pathogenesis of various myeloid malignancies characterized by ineffective erythropoiesis, such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). However, the function and mechanism of IDH1 in human erythropoiesis still remains unclear. Here, utilizing the human erythropoiesis system, we present an evidence of IDH1-mediated chromatin state reprogramming besides its well-characterized metabolism effects. We found that knockdown IDH1 induced chromatin reorganization and subsequently led to abnormalities biological events in erythroid precursors, which could not be rescued by addition of reactive oxygen species (ROS) scavengers or supplementation of α-ketoglutarate (α-KG).We further revealed that knockdown IDH1 induces genome-wide changes in distribution and intensity of multiple histone marks, among which H3K79me3 was identified as a critical factor in chromatin state reprogramming. Integrated analysis of ChIP-seq, ATAC-seq, and RNA-seq recognized that SIRT1 was the key gene affected by IDH1 deficiency. Thus, our current work provided novel insights for further clarifying fundamental biological function of IDH1 which has substantial implications for an in-depth understanding of pathogenesis of diseases with IDH1 dysfunction and accordingly development of therapeutic strategies.https://elifesciences.org/articles/100406IDH1chromatin stateshuman erythropoiesisH3K79me3SIRT1 |
| spellingShingle | Mengjia Li Hengchao Zhang Xiuyun Wu Mengqi Yu Qianqian Yang Lei Sun Wei Li Zhongxing Jiang Fumin Xue Ting Wang Xiuli An Lixiang Chen IDH1 regulates human erythropoiesis by eliciting chromatin state reprogramming eLife IDH1 chromatin states human erythropoiesis H3K79me3 SIRT1 |
| title | IDH1 regulates human erythropoiesis by eliciting chromatin state reprogramming |
| title_full | IDH1 regulates human erythropoiesis by eliciting chromatin state reprogramming |
| title_fullStr | IDH1 regulates human erythropoiesis by eliciting chromatin state reprogramming |
| title_full_unstemmed | IDH1 regulates human erythropoiesis by eliciting chromatin state reprogramming |
| title_short | IDH1 regulates human erythropoiesis by eliciting chromatin state reprogramming |
| title_sort | idh1 regulates human erythropoiesis by eliciting chromatin state reprogramming |
| topic | IDH1 chromatin states human erythropoiesis H3K79me3 SIRT1 |
| url | https://elifesciences.org/articles/100406 |
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