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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Feb 19, 2024 |
| Title |
Mi-2β promotes immune evasion in melanoma by activating EZH2 methylation |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Recent development of new immune checkpoint inhibitors has been particularly successfully in cancer treatment, but still the majority patients fail to benefit. Converting resistant tumors to immunotherapy sensitivity will provide a significant improvement in patient outcome. Here we identify Mi-2β as a key melanoma-intrinsic effector regulating the adaptive anti-tumor immune response. Genetically engineered mouse melanoma studies indicate that loss of Mi-2β rescued the immune response to immunotherapy in vivo. Mechanistically, ATAC-seq indicate that Mi-2β controlled the accessibility of IFN-γ-stimulated genes (ISGs). Mi-2β bound to EZH2 and promote K510 methylation of EZH2 and subsequently activate the trimethylation of H3K27 to inhibit the transcription of ISGs. Finally, we develop an Mi-2β-targeted inhibitor, Z36-MP5, which targeted inhibition of Mi-2β ATPase activity and recovered ISG transcription. Consequently, Z36-MP5 efficiently induce a response to immunotherapy in otherwise resistant melanomas. Our work provides a potential therapeutic strategy to convert immunotherapy resistant melanomas to sensitive ones.
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| Overall design |
Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) indicate that Mi-2β controlled the accessibility of IFN-γ-stimulated genes (ISGs). Mi-2β bound to EZH2 and promote K510 methylation of EZH2 and subsequently activate the trimethylation of H3K27 to inhibit the transcription of ISGs.
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| Contributor(s) |
Li C, Li Y, Xu Z, Jian Y |
| Citation(s) |
38461299 |
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| Submission date |
Feb 14, 2024 |
| Last update date |
Mar 20, 2024 |
| Contact name |
Zhixiang Xu |
| E-mail(s) |
zhixiangxu08@gmail.com
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| Phone |
+8613270538760
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| Organization name |
河南大学
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| Street address |
Jin Ming Avenue north section
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| City |
kaifeng |
| ZIP/Postal code |
475004 |
| Country |
China |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA1076516 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE255782_RAW.tar |
1.7 Gb |
(http)(custom) |
TAR (of BW, NARROWPEAK) |
| GSE255782_merge_peak.bed.gz |
296.5 Kb |
(ftp)(http) |
BED |
SRA Run Selector |
| Raw data are available in SRA |
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