GSE113194 Human ZNF341 deficiency underlies a recessive form of hyper IgE syndrome by disrupting STAT3 transcription-dependent STAT3 activity

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 trans cription-dependent auto-induction and sustained activity of STAT3.

Source: GEO: Gene Expression Omnibus - May 30, 2018 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing Homo sapiens Source Type: research