Interferon signature in patients with STAT1 gain-of-function mutation is epigenetically determined

European Journal of Immunology
Epp KalevisteKai Kisand

Abstract

STAT1 gain-of-function (GOF) variants lead to defective Th17 cell development and chronic mucocutaneous candidiasis (CMC), but frequently also to autoimmunity. Stimulation of cells with STAT1 inducing cytokines like interferons (IFN) result in hyperphosphorylation and delayed dephosphorylation of GOF STAT1. However, the mechanism how the delayed dephosphorylation exactly causes the increased expression of STAT1-dependent genes, and how the intracellular signal transduction from cytokine receptors is affected, remains unknown. In this study we show that the circulating levels of IFN-α were not persistently elevated in STAT1 GOF patients. Nevertheless, the expression of interferon signature genes was evident even in the patient with low or undetectable serum IFN-α levels. Chromatin immunoprecipitation (ChIP) experiments revealed that the active chromatin mark trimethylation of lysine 4 of histone 3 (H3K4me3), was significantly enriched in areas associated with interferon-stimulated genes in STAT1 GOF cells in comparison to cells from healthy donors. This suggests that the chromatin binding of GOF STAT1 variant promotes epigenetic changes compatible with higher gene expression and elevated reactivity to type I interferons, and pos...Continue Reading

References

Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·S D DerR H Silverman
Apr 12, 2003·Leukemia & Lymphoma·H Al-ZahraniJ H Lipton
Mar 9, 2005·Proceedings of the National Academy of Sciences of the United States of America·Minghao ZhongJames E Darnell
Dec 22, 2009·Journal of Autoimmunity·Yaron Tomer
May 4, 2010·Nature Biotechnology·Cory Y McLeanGill Bejerano
Jan 12, 2011·Nature Biotechnology·James T RobinsonJill P Mesirov
Jul 1, 2011·The New England Journal of Medicine·Frank L van de VeerdonkMihai G Netea
Jul 6, 2011·The Journal of Experimental Medicine·Luyan LiuJean-Laurent Casanova
Jan 26, 2012·PloS One·Thomas DerrienPaolo Ribeca
Mar 6, 2012·Nature Methods·Ben Langmead, Steven L Salzberg
Nov 28, 2012·Cell·Golnaz VahediJohn J O'Shea
Sep 24, 2013·JAK-STAT·Greg M Delgoffe, Dario A A Vignali
Nov 26, 2013·Nucleic Acids Research·Donna KarolchikW James Kent
Dec 18, 2013·Journal of Leukocyte Biology·Yoko MizoguchiMasao Kobayashi
Oct 8, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yasuhiro YamazakiTadashi Ariga
Feb 20, 2015·Nature·UNKNOWN Roadmap Epigenomics ConsortiumManolis Kellis
Mar 11, 2015·Endocrinology, Diabetes & Metabolism Case Reports·J Rajkanna, S O Oyibo
Jul 15, 2015·Proceedings of the National Academy of Sciences of the United States of America·Chi-Keung WanWarren J Leonard
Jan 21, 2016·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Rotraut MössnerTimo Buhl
Mar 13, 2016·European Journal of Immunology·Tania O CrișanLeo A B Joosten
Apr 22, 2016·Nucleic Acids Research·Jüri ReimandJaak Vilo
Apr 23, 2016·Science·Mihai G NeteaRamnik J Xavier
Apr 27, 2016·Blood·Julie ToubianaUNKNOWN International STAT1 Gain-of-Function Study Group
Nov 9, 2016·The Journal of Experimental Medicine·Mathieu P Rodero, Yanick J Crow
Feb 2, 2017·Annual Review of Immunology·Romain BanchereauVirginia Pascual
Mar 23, 2017·Nature Immunology·Alejandro V VillarinoJohn J O'Shea

❮ Previous
Next ❯

Citations

Jul 30, 2019·Frontiers in Immunology·Ofer ZimmermanSteven M Holland
Sep 13, 2019·Journal of Clinical Immunology·Tariq Al ShehriTimothy R Leahy
Jun 26, 2020·Frontiers in Immunology·Simone GiovannozziRik Schrijvers
Apr 3, 2021·Cellular & Molecular Immunology·Georgios SogkasReinhold Ernst Schmidt
May 12, 2021·Pediatric Rheumatology Online Journal·Martina GirardelliAlberto Tommasini
Jun 5, 2021·The Journal of Allergy and Clinical Immunology·David HaginNatalia T Freund
Aug 22, 2021·Stem Cell Reviews and Reports·Han SunLisha Li
Nov 6, 2021·Pediatric Allergy and Immunology : Official Publication of the European Society of Pediatric Allergy and Immunology·Ori ScottChaim M Roifman

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Signaling & Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. This feed covers the latest research on signaling and epigenetics in cell growth and cancer.

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.