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CRL4-DCAF15 control of cohesin dynamics sustains cell proliferation [RNA-seq_CRISPR]

GSE241578 Homo sapiens (human) RNA-seq (gene expression) 18 samples Submitted 2024/05/22 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 18 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Samples
18 samples: 6 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
DCAF15 control of cohesin dynamics sustains acute myeloid leukemiaNature communications · 2024
Summary (written by the submitters)
The CRL4-DCAF15 E3 ubiquitin ligase complex is targeted by the aryl-sulfonamide molecular glues, leading to neo-substrate recruitment, ubiquitination, and proteasomal degradation. However, the physiological function of DCAF15 remains unknown. Using a domain-focused genetic screening approach, we reveal DCAF15 as an acute myeloid leukemia (AML)-biased dependency.
Read the full summary ↓
Loss of DCAF15 results in suppression of AML through compromised replication fork integrity and consequent accumulation of DNA damage. Accordingly, DCAF15 loss sensitizes AML to replication stress-inducing therapeutics. Mechanistically, we discover that DCAF15 directly interacts with the SMC1A protein of the cohesin complex and destabilizes the cohesin regulatory factors PDS5A and CDCA5. Loss of PDS5A and CDCA5 removal precludes cohesin acetylation on chromatin, resulting in uncontrolled chromatin loop extrusion, defective DNA replication, and apoptosis. Collectively, our findings uncover an endogenous, cell autonomous function of DCAF15 in sustaining AML proliferation through post-translational control of cohesin dynamics.
Published in
DCAF15 control of cohesin dynamics sustains acute myeloid leukemia
Grothusen GP, Chang R, Cao Z et al. · Nature communications 2024 · PMID 38961054 · doi:10.1038/s41467-024-49882-x
This dataset
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.

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 GSE241578_RAW.tar (it can run to tens of gigabytes).

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.

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1008731 and SRA study SRP456806. Searching any of these in the dataset finder brings you back here.

Study design
6 conditions, mostly in triplicate
MV4-11 cells, LRG2.1-sgROSA26(Control), LRChe… ×3 MV4-11 cells, LRG2.1-sgROSA26(Control), LRChe… ×3 MV4-11 cells, LRG2.1-sgTP53#6, LRCherry2.1-sg… ×3 MV4-11 cells, LRG2.1-sgTP53#6, LRCherry2.1-sg… ×3 HEL cells, LRCherry2.1-sgROSA26(Control), ×3 HEL cells, LRCherry2.1-sgDCAF15#2, ×3

Supports a between-group comparison across 18 samples.

How we read this: 6 replicated groups read from 18 sample titles; they account for 18 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
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