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Series GSE186244 Query DataSets for GSE186244
Status Public on Nov 01, 2022
Title Human DUX4 and mouse Dux interact with STAT1 and broadly inhibit interferon-stimulated gene induction
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary DUX4 activates the first wave of zygotic gene expression in the early embryo. Mis-expression of DUX4 in skeletal muscle causes facioscapulohumeral dystrophy (FSHD), whereas expression in cancers suppresses IFNg-induction of MHC Class I and contributes to immune evasion. We show that the DUX4 protein broadly suppresses immune signaling pathways—including IFNg, IFNb, DDX58, IFIH1 and cGAS mediated pathways. A conserved region containing (L)LxxL(L) motifs in the DUX4 carboxyterminal domain (CTD) was necessary to suppress interferon stimulated genes (ISGs). Co-immunoprecipitation identified DUX4-CTD interaction with multiple immune signaling factors, including STAT1. The DUX4-CTD (L)LxxL(L) region interacts with phosphorylated STAT1, sequesters it in the nucleus, modestly reduces its DNA binding, and prevents STAT1 from inducing ISG transcription. Mouse Dux similarly interacted with STAT1 and suppressed IFNg induction of ISGs. These findings identify an evolved role of the DUXC family in modulating immune signaling pathways with implications for development, cancers, and FSHD.
Overall design Examination of mRNA expression in two DUX4 mutants, F67A and aa154-424
Contributor(s) Spens A, Bennett S, Tapscott SJ
Citation(s) 37092726
Submission date Oct 20, 2021
Last update date May 10, 2023
Contact name Stephen Tapscott
Organization name Fred Hutchinson Cancer Research Center
Street address 1100 Fairview Ave N, Room C3-123
City Seattle
State/province Washington
ZIP/Postal code 98109
Country USA
Platforms (1)
GPL30173 NextSeq 2000 (Homo sapiens)
Samples (18)
GSM5641615 F67A_c6_IFNg1_S4
GSM5641616 F67A_c6_IFNg2_S5
GSM5641617 F67A_c6_IFNg3_S6
BioProject PRJNA773067
SRA SRP342322

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Supplementary file Size Download File type/resource
GSE186244_countsAA154-424.csv.gz 644.7 Kb (ftp)(http) CSV
GSE186244_countsF67A.csv.gz 645.1 Kb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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