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AgRP neuron epigenomes across hunger states reveal that IRF3 mediates leptin's effects

GSE240484 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 46 samples Submitted 2024/04/12 Platform GPL19057
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 46 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
Mus musculus (mouse)
Samples
46 samples: 14 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
AgRP neuron cis-regulatory analysis across hunger states reveals that IRF3 mediates leptin's acute effectsNature communications · 2024
Summary (written by the submitters)
AgRP neurons in the arcuate nucleus of the hypothalamus (ARC) coordinate homeostatic changes in appetite associated with fluctuations in food availability and leptin signaling. Identifying the relevant transcriptional regulatory pathways in these neurons has been a priority, yet such attempts have been stymied due to their low abundance and the rich cellular diversity of the ARC.
Read the full summary ↓
Here we generated male mouse AgRP neuron-specific transcriptomic and chromatin accessibility profiles during three distinct hunger states of satiety, fasting-induced hunger, and leptin-induced hunger suppression. Cis-regulatory analysis of these integrated datasets enabled the identification of 28 putative hunger-promoting and 29 putative hunger-suppressing transcriptional regulators in AgRP neurons, 16 of which were predicted to be transcriptional effectors of leptin. Within our dataset, Interferon regulatory factor 3 (IRF3) emerged as a leading candidate mediator of leptin-induced hunger-suppression. Gain- and loss-of-function experiments in vivo confirm the role of IRF3 in mediating the acute satiety-evoking effects of leptin in AgRP neurons, while live-cell imaging in vitro indicate that leptin can activate neuronal IRF3 in a cell autonomous manner. Finally, we employ CUT&RUN to uncover direct transcriptional targets of IRF3 in AgRP neurons in vivo. Thus, our findings identify AgRP neuron-expressed IRF3 as a key transcriptional effector of the hunger-suppressing effects of leptin.
Published in
AgRP neuron cis-regulatory analysis across hunger states reveals that IRF3 mediates leptin's acute effects
Heyward FD, Liu N, Jacobs C et al. · Nature communications 2024 · PMID 38821928 · doi:10.1038/s41467-024-48885-y
This dataset
Open GSE240484 in finder → Find more mouse RNA-seq 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 GSE240484_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 PRJNA1003890 and SRA study SRP454286. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38821928) ↗
Study design
14 conditions, mostly in duplicate
AgRP neurons, fasted, RNA, ×4 AgRP neurons, leptin, RNA, ×4 arcuate nucleus, fasted, RNA, ×4 arcuate nucleus, fed, RNA, ×4 arcuate nucleus, leptin, RNA, ×4 AgRP neurons, fed, RNA, ×3 POMC neurons, fasted, RNA, ×2 POMC neurons, fed, RNA, ×2 +13 more

Supports a between-group comparison across 39 samples.

How we read this: 14 replicated groups read from 46 sample titles; they account for 39 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

+ 6 more — browse all 46 samples with per-sample file links →

Datasets on a similar topic

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