GEO series
Remodeling of Il4-Il13-Il5 locus underlies selective gene expression (ATAC-Seq)
GSE266341
Homo sapiens; Mus musculus
Genome binding/occupancy profiling by high throughput sequencing
21 samples
Submitted 2024/09/27
Platform GPL24247Platform GPL24676
Summary
The type 2 cytokines, interleukin (IL)-4, IL-5 and IL-13 reside within a multi-gene cluster in mammals. These cytokines represent the hallmark of type 2 immune responses controlling parasites and promoting tissue repair, as well as causing allergic diseases. Both innate and adaptive lymphocytes secrete type 2 cytokines with discordant production spectra. We took a holistic structural and functional view of the type 2 cytokine locus before and after activation, comparing innate (ILC2) and adaptive (Th2) lymphocytes to understand mechanisms underlying their distinctive programs. Rapid induction of IL-5 dominates in ILC2, whereas IL-4 does so in Th2 cells. Using high-resolution chromatin conformation capture we found that global cellular chromatin architecture remained constant, whereas the type 2 cytokine locus rapidly remodeled. In ILC2, Il13 and Il5 loci were aligned in proximity whereas Il4 locus was insulated. In Th2 cells, Il4 and Il13 positioned in proximity while the Il5 locus remained distal. Select REs were individually deleted in mice to confirm cell-type specific and activation-dependent roles in type 2 responses in vivo. Thus, contrary to the premise that chromatin architecture plays a minimal role in steady-state gene induction, signal-dependent remodeling of 3D configuration underlies the discordant cytokine outputs in ILC2s versus Th2 cells.
Published in
Nagashima H, Shayne J, Jiang K et al.
· Nature immunology 2024
· PMID 39567762
· doi:10.1038/s41590-024-02007-4
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE266341_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 21 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1106801 and SRA study SRP505191. Searching any of these in the dataset finder brings you back here.
Study design
21 conditions, each sampled once — no replicated groups
Read from 21 sample titles: 21 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM8245254 HN_ATAC_037_human_naiveTh_donor1
- GSM8245255 HN_ATAC_038_human_naiveTh_donor2
- GSM8245256 HN_ATAC_039_human_naiveTh_donor3
- GSM8245257 HN_ATAC_040_human_invitroTh2_nostim_donor1
- GSM8245258 HN_ATAC_041_human_invitroTh2_nostim_donor2
- GSM8245259 HN_ATAC_042_human_invitroTh2_nostim_donor3
- GSM8245260 HN_ATAC_043_human_invitroTh2_PI_4h_donor1
- GSM8245261 HN_ATAC_044_human_invitroTh2_PI_4h_donor2
- GSM8245262 HN_ATAC_045_human_invitroTh2_PI_4h_donor3
- GSM8245263 HN_ATAC_046_ILC2_WT_nostim_4h_rep1
- GSM8245264 HN_ATAC_047_ILC2_WT_nostim_4h_rep2
- GSM8245265 HN_ATAC_048_ILC2_WT_nostim_4h_rep3
- GSM8245266 HN_ATAC_049_ILC2_6.5kbIl13KO_nostim_4h_rep1
- GSM8245267 HN_ATAC_050_ILC2_6.5kbIl13KO_nostim_4h_rep2
- GSM8245268 HN_ATAC_051_ILC2_6.5kbIl13KO_nostim_4h_rep3
- GSM8245269 HN_ATAC_052_ILC2_WT_IL33_NMU_4h_rep1
- GSM8245270 HN_ATAC_053_ILC2_WT_IL33_NMU_4h_rep2
- GSM8245271 HN_ATAC_054_ILC2_WT_IL33_NMU_4h_rep3
- GSM8245272 HN_ATAC_055_ILC2_6.5kbIl13KO_IL33_NMU_4h_rep1
- GSM8245273 HN_ATAC_056_ILC2_6.5kbIl13KO_IL33_NMU_4h_rep2
- GSM8245274 HN_ATAC_057_ILC2_6.5kbIl13KO_IL33_NMU_4h_rep3
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