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Chromatin-associated LTR RNA m5C oxidation by TET2 regulates chromatin state and leukemogenesis [seq_DNA-CUTandTag]

GSE269959 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 41 samples Submitted 2024/07/25 Platform GPL24676Platform GPL24247
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 41 samples

What it is
ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism
Homo sapiens (human)
Samples
41 samples: 14 conditions, mostly in triplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
RNA m(5)C oxidation by TET2 regulates chromatin state and leukaemogenesisNature · 2024
Summary (written by the submitters)
Mutation of Ten-eleven translocation enzyme 2 (TET2) drives myeloid malignancy initiation and progression. TET2 deficiency is known to cause a globally opened chromatin state and activation of genes contributing to aberrant hematopoietic stem cell self-renewal. However, the open chromatin observed in TET2-deficient mouse embryonic stem cells, leukemic cells and hematopoietic progenitor and stem cells is inconsistent with the designated role of DNA 5mC oxidation of TET2.
Read the full summary ↓
We show here that chromatin-associated retrotransposon RNA 5-methylcytosine (m5C) can be recognized by the methyl-CpG-binding domain protein MBD6, which guides deubiquitination of nearby histone H2AK119ub to promote an open chromatin state. TET2 oxidizes m5C and antagonizes this MBD6-dependent H2AK119ub deubiquitination. Thereby, TET2 depletion leads to globally decreased H2AK119ub, more open chromatin, and increased transcription in stem cells. TET2 mutant human leukemia becomes dependent on this gene activation pathway, with MBD6 depletion selectively blocks proliferation of TET2 mutant leukemic cells and fully reverses the hematopoiesis defects caused by Tet2 loss, both in vitro and in vivo. Altogether, our findings reveal a 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.
Published in
RNA m(5)C oxidation by TET2 regulates chromatin state and leukaemogenesis
Zou Z, Dou X, Li Y et al. · Nature 2024 · PMID 39358506 · doi:10.1038/s41586-024-07969-x
This dataset
Open GSE269959 in finder → Find more ChIP / ATAC / CUT&Tag datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE269959_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1124380 and SRA study SRP514151. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39358506) ↗
Study design
14 conditions, mostly in triplicate
mESC, WT, H2AK119ub, CUT&Tag, ×3 mESC, Tet2 KO, H2AK119ub, CUT&Tag, ×3 mESC, WT; siNC, H2AK119ub, CUT&Tag, ×3 mESC, Tet2 KO; siNC, H2AK119ub, CUT&Tag, ×3 mESC, Tet2 KO; siMbd6, H2AK119ub, CUT&Tag, ×3 mESC, Tet2 KO; siNsun2, H2AK119ub, CUT&Tag, ×3 mHSPC, WT; shNC, H2AK119ub, CUT&Tag, ×3 mHSPC, Tet2 KO; shNC, H2AK119ub, CUT&Tag, ×3 +6 more

Supports a between-group comparison across 41 samples.

How we read this: 14 replicated groups read from 41 sample titles; they account for 41 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

+ 1 more — browse all 41 samples with per-sample file links →

Datasets on a similar topic

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