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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jul 25, 2024 |
| Title |
TET2 regulates histone H2AK119ub and leukemogenesis through LTR RNA m5C oxidation [seq_DNA-CUTandTag] |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Mutation of TET2 drives myeloid malignancy progression. TET2 deficiency is known to cause a globally opened chromatin and activation of genes contributing to aberrant HSPC self-renewal. We show here that chromatin-associated retrotransposon RNA 5-methylcytosine (m5C), installed by NSUN2, can be recognized by the methyl-CpG-binding domain protein MBD6, which guides deubiquitylation of nearby histone H2AK119ub to promote an open chromatin state. TET2 oxidizes m5C and antagonizes this MBD6-dependent H2AK119ub deubiquitylation. Thereby, TET2 depletion leads to globally decreased H2AK119ub, more open chromatin, and increased transcription in stem cells. TET2 mutant human leukemia became dependent on this gene activation pathway, with MBD6 silencing selectively inhibits proliferation of TET2 mutant leukemia in vitro and in vivo. Altogether, our findings reveal a previously unknown chromatin regulation pathway by TET2 through retrotransposon RNA m5C oxidation and identify the downstream MBD6 protein as a feasible target for developing therapies specific against TET2 mutant malignancies.
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| Overall design |
CUT&Tag-seq in mESC, mouse LK and K562 cells
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| Contributor(s) |
Zou Z, Dou X, He C |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Aug 21, 2023 |
| Last update date |
Jul 26, 2024 |
| Contact name |
Xiaoyang Dou |
| E-mail(s) |
xiaoyang.dou@sibcb.ac.cn
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| Organization name |
Center for Excellence in Molecular Cell Science, CAS
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| Street address |
320 Yue Yang Road
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| City |
Shanghai |
| ZIP/Postal code |
200031 |
| Country |
China |
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| Platforms (2) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (24)
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| GSM7720826 |
mESC, Tet2 WT, H2AK119ub, CUT&Tag, rep1 |
| GSM7720827 |
mESC, Tet2 WT, H2AK119ub, CUT&Tag, rep2 |
| GSM7720828 |
mESC, Tet2 KO, H2AK119ub, CUT&Tag, rep1 |
| GSM7720829 |
mESC, Tet2 KO, H2AK119ub, CUT&Tag, rep2 |
| GSM7720830 |
mESC, Tet2 WT, H3K27me3, CUT&Tag, rep1 |
| GSM7720831 |
mESC, Tet2 WT, H3K27me3, CUT&Tag, rep2 |
| GSM7720832 |
mESC, Tet2 KO, H3K27me3, CUT&Tag, rep1 |
| GSM7720833 |
mESC, Tet2 KO, H3K27me3, CUT&Tag, rep2 |
| GSM7720834 |
mLK, Tet2 WT, H2AK119ub, CUT&Tag, rep1 |
| GSM7720835 |
mLK, Tet2 WT, H2AK119ub, CUT&Tag, rep2 |
| GSM7720836 |
mLK, Tet2 KO, H2AK119ub, CUT&Tag, rep1 |
| GSM7720837 |
mLK, Tet2 KO, H2AK119ub, CUT&Tag, rep2 |
| GSM7720838 |
mLK, Tet2 WT, H3K27me3, CUT&Tag, rep1 |
| GSM7720839 |
mLK, Tet2 WT, H3K27me3, CUT&Tag, rep2 |
| GSM7720840 |
mLK, Tet2 KO, H3K27me3, CUT&Tag, rep1 |
| GSM7720841 |
mLK, Tet2 KO, H3K27me3, CUT&Tag, rep2 |
| GSM7720842 |
K562, siControl, H2AK119ub, CUT&Tag, rep1 |
| GSM7720843 |
K562, siControl, H2AK119ub, CUT&Tag, rep2 |
| GSM7720844 |
K562, siMBD6, H2AK119ub, CUT&Tag, rep1 |
| GSM7720845 |
K562, siMBD6, H2AK119ub, CUT&Tag, rep2 |
| GSM7720846 |
K562, TET2 WT, H2AK119ub, CUT&Tag, rep1 |
| GSM7720847 |
K562, TET2 WT, H2AK119ub, CUT&Tag, rep2 |
| GSM7720848 |
K562, TET2 KO, H2AK119ub, CUT&Tag, rep1 |
| GSM7720849 |
K562, TET2 KO, H2AK119ub, CUT&Tag, rep2 |
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| This SubSeries is part of SuperSeries: |
| GSE241347 |
Chromatin-associated LTR RNA m5C oxidation by TET2 regulates leukemogenesis |
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| Relations |
| BioProject |
PRJNA1007667 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE241304_RAW.tar |
37.9 Mb |
(http)(custom) |
TAR (of BED) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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