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| Status |
Public on May 20, 2024 |
| Title |
Glycolysis involved in transcription dysregulation through histone lactylation in T-lineage acute lymphoblastic leukemia II |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Tumor cells are known for excessive lactate production, due to Warburg effect, and transcriptional dysregulation. However, how lactate influences the epigenetic modifications at a genome-wide level and its impact on gene transcription in tumor cell remains unclear. Addressing this gap, we analyzed genome-wide modification of H3K18 lactylation (H3K18la) in T-cell acute lymphoblastic leukemia (T-ALL). Integrated analysis with histone modifications with established functions show the H3K18la is mainly involved in active regulation of gene transcription. We report increased lactate and H3K18la modification levels in T-ALL as compared to normal T cells. We observe clusters of H3K18la modifications in patterns reminiscent of super-enhancers. We show a notable shift of genome-wide H3K18la modification from T cell immunity in normal T cells to leukemogenesis in T-ALL, correlating with altered gene transcription profiles. By disrupting H3K18la modification, we uncover both synergetic and divergent changes between H3K18la and H3K27ac modifications, suggesting the H3K18la and H3K27ac modifications may have specific regulation mechanisms correspondingly. These findings expand our understanding of metabolic disruptions involvement in transcription dysregulation through epigenetic changes in T-ALL, and emphasize the collective importance of histone modifications in maintaining oncogenic epigenetic stability.
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| Overall design |
To explore the effects of H3K18la modifications on transcriptional regulation, we subjected JURKAT cells to RNA sequencing (RNA-Seq) across three experimental conditions: control (untreated), oxamate treatment, and combined oxamate and lactate treatment.
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| Contributor(s) |
Wu W, Sun H, Wang H, Wu X, Cui B, Zhao S, Fan R, Wang R, Zhong Y, Wang Y, Wu K, Chen X, Zheng L, shen S, Yin M, Liu Y |
| Citation missing |
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| Submission date |
Apr 10, 2024 |
| Last update date |
May 20, 2024 |
| Contact name |
Wu Wenyan |
| E-mail(s) |
estheryan@sjtu.edu.cn
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| Organization name |
Shanghai Children's Medical Center
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| Street address |
1678 Dongfang Road, Pudong New District, Shanghai
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| City |
Shanghai |
| ZIP/Postal code |
200127 |
| Country |
China |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA1098754 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE263697_normalized_counts.txt.gz |
140.1 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
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