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Transcriptome profiling based on the presence of Usf2 and nutrient starvation

GSE252311 Mus musculus (mouse) RNA-seq (gene expression) 16 samples Submitted 2024/08/06 Platform GPL21103Platform GPL28430
At a glance

RNA-seq (gene expression) · mouse · 16 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
Mus musculus (mouse)
Samples
16 samples: 8 conditions, mostly in duplicateGroups 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
USF2 and TFEB compete in regulating lysosomal and autophagy genesNature communications · 2024
Summary (written by the submitters)
Intricate regulation of lysosome and autophagy processes is essential for maintaining cellular homeostasis and basal metabolism. While the consequences of disrupting or attenuating lysosome and autophagy systems have been extensively studied, little is known about the impact of hyper-activation of lysosomal and autophagy genes on homeostasis.
Read the full summary ↓
Our research uncovers previously unknown transcriptional repression mechanism by upstream stimulatory factor 2 (USF2), which inhibits lysosomal and autophagy genes in nutrient-rich conditions. USF2 binds to the CLEAR motif within lysosomal genes along with HDAC1, which diminishes H3K27 acetylation levels, restrains chromatin accessibility, and lowers lysosomal gene expression. Under starvation, USF2 competes with TFEB, a master transcriptional activator of lysosomal and autophagy genes, to bind target gene promoters in phosphorylation-dependent manner. Phosphorylation of the S155 site by GSK3b plays a pivotal role in controlling USF2's DNA binding activity for the repression of lysosomal genes while GSK3b-mediated phosphorylation of TFEB enhances its cytoplasmic retention. Applying these discoveries has potential for treating diseases associated with protein aggregation, including alpha-1 antitrypsin deficiency. These findings demonstrate that the USF2 repression mechanism could be a potent therapeutic strategy for various lysosome and autophagy-related diseases.
Published in
USF2 and TFEB compete in regulating lysosomal and autophagy genes
Kim J, Yu YS, Choi Y et al. · Nature communications 2024 · PMID 39333072 · doi:10.1038/s41467-024-52600-2
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 GSE252311_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 PRJNA1059624 and SRA study SRP480811. Searching any of these in the dataset finder brings you back here.

Study design
8 conditions, mostly in duplicate
Usf2 WT MEF, Normal media, ×2 Usf2 WT MEF, Amino acid starvation media, ×2 Usf2 KO MEF, Normal media, ×2 Usf2 KO MEF, Amino acid starvation media, ×2 WT MEF, Normal media, ×2 WT MEF, Glucose starvation media, ×2 Usf2-/- MEF, Normal media, ×2 Usf2-/- MEF, Glucose starvation media, ×2

Supports a between-group comparison across 16 samples.

How we read this: 8 replicated groups read from 16 sample titles; they account for 16 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
Datasets on a similar topic

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