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CRISPR-Cas screen in ILC2 identifies Mef2d as a regulator of GATA3 and type-2 immunity [ChIP-Seq]

GSE242030 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 17 samples Submitted 2024/07/03 Platform GPL21103Platform GPL30172
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 17 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
17 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
Mef2d potentiates type-2 immune responses and allergic lung inflammationScience (New York, N.Y.) · 2024
Summary (written by the submitters)
Group 2 innate lymphoid cells (ILC2s) orchestrate tissue homeostasis, allergic disorders and anti-helminth protective immunity through their production of cytokines. However, their rarity has hampered high-throughput genetic screening approaches to uncover novel ILC2 regulators in an unbiased manner. We combined expansion of progenitors from multi-reporter mouse strains with optimised ILC differentiation cultures to perform CRISPR-Cas9 screens for regulators of ILC2 development and function.
Read the full summary ↓
Mef2d emerged as a critical regulator of GATA3 and IL-13, and was essential for type-2 immunity as demonstrated by conditional Mef2d-deficient mice, including a Boolean-ILC2-Cre (BIC) mouse strain developed to enable ILC2-specific gene deletion. Mechanistically, Mef2d bound and transcriptionally repressed the Zc3h12a locus encoding the endonuclease Regnase-1, a negative regulator of IL-33 receptor (ST2) and GATA3 expression, thereby promoting IL-33-mediated ILC2 proliferation and cytokine production. Notably, in ILC2s Mef2d also acted downstream of leukotriene C4-induced calcium-mediated signalling to translocate NFAT1 to the nucleus to promote type-2 gene transcription. These Mef2d-mediated pathways converge and feedback to potentiate type-2 immunity.
Published in
Mef2d potentiates type-2 immune responses and allergic lung inflammation
Szeto ACH, Clark PA, Ferreira ACF et al. · Science (New York, N.Y.) 2024 · PMID 38935708 · doi:10.1126/science.adl0370
This dataset
Open GSE242030 in finder → Find more mouse 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 GSE242030_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 PRJNA1011237 and SRA study SRP457769. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38935708) ↗
Study design
6 conditions, mostly in triplicate
ILC2_anti-Mef2d ×3 ILC2_anti-NFAT1 ×3 ILC2_LTC4_anti-NFAT1 ×3 ILC2_anti-GATA3 ×2 Th2_anti-Mef2d ×2 Th2_anti-NFAT1 ×2 ILC2_Input ×1 Th2_Input ×1

Supports a between-group comparison across 15 samples.

How we read this: 6 replicated groups read from 17 sample titles; they account for 15 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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