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Status |
Public on May 30, 2018 |
Title |
A recessive form of hyper-IgE syndrome by disruption of ZNF341-dependent STAT3 transcription and activity |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing
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Summary |
Heterozygosity for human STAT3 dominant-negative (DN) mutations underlies an autosomal dominant form of hyper-IgE syndrome (HIES). We describe patients with an autosomal recessive form of HIES due to loss-of-function mutations of a previously uncharacterized gene, ZNF341. ZNF341 is a transcription factor that resides in the nucleus, where it binds a specific DNA motif present in various genes, including, most notably the STAT3 promoter. The patients’ cells have low basal levels of STAT3 mRNA and protein. The auto-induction of STAT3 production, activation, and function by STAT3-activating cytokines is particularly strongly impaired. Like patients with STAT3 DN mutations, ZNF341-deficient patients lack Th17 cells, have an excess of Th2 cells, and low memory B cells, due to the tight dependence of STAT3 activity on ZNF341 in lymphocytes. Their milder extra-hematopoietic manifestations and stronger inflammatory responses reflect the lower ZNF341-dependence of STAT3 activity in other cell types. Human ZNF341 is essential for the STAT3 transcription-dependent auto-induction and sustained activity of STAT3.
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Overall design |
RNA-Seq and ChIP-Seq analyses using freshly isolated CD3+ T cells or EBV-B cells transduced with ZNF341 WT isoform 1 (NM_001282933) or 2 (NM_032819) or an empty vector (EV) from the same patient (P4).
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Web link |
https://www.ncbi.nlm.nih.gov/pubmed/29907691
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Contributor(s) |
Beziat V, Li J, Lin J, Ma CS, Li P, Bousfiha A, Pellier I, Zoghi S, Baris S, Keles S, Gray P, Du N, Yang Y, Zerbib Y, Levy R, Leclercq T, About F, Lim A, Rao G, Payne K, Pelham SJ, Avery DT, Deenick EK, Pillay B, Chou J, Guery R, Belkadi A, Guerin A, Migaud M, Rattina V, Ailal F, Benhsaien I, Bouaziz M, Tanwir H, Chaussabel D, Marr N, El Benna J, Grimbacher B, Wargon O, Bustamante JC, Boisson B, Muller-Fleckenstein I, Fleckenstein B, Chandesris M, Titeux M, Fraitag S, Alyanakian M, Leruez-Ville M, Picard C |
Citation(s) |
29907691 |
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Submission date |
Apr 16, 2018 |
Last update date |
Mar 27, 2019 |
Contact name |
Peng Li |
E-mail(s) |
peng.li@nih.gov
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Organization name |
NIH
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Department |
NHLBI
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Lab |
LMI
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Street address |
9000 Rockville Pike
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City |
Bethesda |
State/province |
MD |
ZIP/Postal code |
20892 |
Country |
USA |
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Platforms (1) |
GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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Samples (11)
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Relations |
BioProject |
PRJNA450407 |
SRA |
SRP140531 |
Supplementary file |
Size |
Download |
File type/resource |
GSE113194_RAW.tar |
1.1 Gb |
(http)(custom) |
TAR (of BEDGRAPH, TXT) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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