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Series GSE242911 Query DataSets for GSE242911
Status Public on Sep 13, 2023
Title STAT4 promotes Bhlhe40 induction to drive protective IFN-g from natural killer cells during viral infection [STAT4 CUT&RUN]
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary NK cells represent a cellular component of the mammalian innate immune system, and mount rapid responses against viral infection, including the secretion of the potent anti-viral effector cytokine IFN-g. Following mouse cytomegalovirus (MCMV) infection, Bhlhe40 was the most highly induced transcription factor in NK cells among the basic helix-loop-helix family. Bhlhe40 upregulation in NK cells depended upon IL-12 and IL-18 signals, with the promoter of Bhlhe40 enriched for STAT4 and the permissive histone H3K4me3, and STAT4-deficient NK cells showing an impairment of Bhlhe40 induction and diminished H3K4me3. Transcriptomic and protein analysis of Bhlhe40-deficient NK cells revealed a defect in IFN-g production during MCMV infection, resulting in diminished protective immunity following viral challenge. Finally, we provide evidence that Bhlhe40 directly promotes IFN-g by binding throughout the Ifng loci in activated NK cells. Thus, our study reveals how STAT4-mediated control of Bhlhe40 drives protective IFN-g secretion by NK cells during viral infection.
Overall design To investigate the binding sites of STAT4 in NK cells during homeostasis and 3 hour IL-12 + IL-18 cytokine stimulation, we performed STAT4 CUT&RUN using WT and STAT4-/-(STAT4KO) mice.
All cells for each conditions were sorted and cultured in complete IMDM + IL-15 media for 5 days prior. These cells were then washed and incubated in complete IMDM media without IL-15 for 1 hour prior to addition of appropriate stimulus, unstimulated or 3 hour IL-12 + IL-18. After stimulation, these CD49b+ NK cells were FACS sorted and CUT&RUN was performed, where replicates are biologically paired across stimulation conditions.
Contributor(s) Kim H, Sun JC
Citation(s) 37830760
Submission date Sep 11, 2023
Last update date Dec 13, 2023
Contact name Hyunu Kim
Phone 3142038957
Organization name Memorial Sloan Kettering Cancer Center
Department Immunology
Lab Joseph Sun lab
Street address 417 E 68th St
City New York
State/province NY
ZIP/Postal code 10065
Country USA
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (10)
GSM7774720 STAT4KO NK cells, unstimulated, non enriched input
GSM7774721 STAT4KO NK cells, stimulated with IL12 + IL18, biol rep 1
GSM7774722 STAT4KO NK cells, stimulated with IL12 + IL18, biol rep 2
This SubSeries is part of SuperSeries:
GSE242914 STAT4 promotes Bhlhe40 induction to drive protective IFN-g from natural killer cells during viral infection
BioProject PRJNA1015269

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE242911_Project_06000OF_STAT4CNR_peakatlas_normCounts.tsv.gz 259.0 Kb (ftp)(http) TSV
GSE242911_RAW.tar 2.2 Gb (http)(custom) TAR (of BW)
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Raw data are available in SRA

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