Promiscuous Gene Expression in the Thymus: A Matter of Epigenetics, miRNA, and More?

Frontiers in Immunology
Olga Ucar, Kristin Rattay

Abstract

The induction of central tolerance in the course of T cell development crucially depends on promiscuous gene expression (pGE) in medullary thymic epithelial cells (mTECs). mTECs express a genome-wide variety of tissue-restricted antigens (TRAs), preventing the escape of autoreactive T cells to the periphery, and the development of severe autoimmunity. Most of our knowledge of how pGE is controlled comes from studies on the autoimmune regulator (Aire). Aire activates the expression of a large subset of TRAs by interacting with the general transcriptional machinery and promoting transcript elongation. However, further factors regulating Aire-independent TRAs must be at play. Recent studies demonstrated that pGE in general and the function of Aire in particular are controlled by epigenetic and post-transcriptional mechanisms. This mini-review summarizes current knowledge of the regulation of pGE by miRNA and epigenetic regulatory mechanisms such as DNA methylation, histone modifications, and chromosomal topology.

References

Sep 15, 1998·Human Molecular Genetics·P BjörsesL Peltonen
Sep 24, 1998·Immunology Today·P PetersonK J Krohn
Mar 26, 2003·The Journal of Biological Chemistry·Astrid MurumägiPärt Peterson
Sep 3, 2004·Nature Reviews. Immunology·Bruno Kyewski, Jens Derbinski
Sep 2, 2005·Nature Reviews. Genetics·Keith D Robertson
Sep 21, 2005·The Journal of Experimental Medicine·Wenyu JiangChristophe Benoist
Nov 23, 2006·The Journal of Experimental Medicine·Jason DeVossMark S Anderson
Mar 21, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Connie M KrawczykEdward J Pearce
Oct 3, 2007·The Journal of Experimental Medicine·Daniel GrayDiane Mathis
Oct 17, 2007·Molecular and Cellular Biology·Irena OvenB Matija Peterlin
Jan 9, 2008·Proceedings of the National Academy of Sciences of the United States of America·Jens DerbinskiBruno Kyewski
May 24, 2008·Molecular Cell·Ulf Andersson ØromAnders H Lund
Sep 11, 2008·Proceedings of the National Academy of Sciences of the United States of America·Mireia Guerau-de-ArellanoChristophe Benoist
Oct 7, 2008·Proceedings of the National Academy of Sciences of the United States of America·Jennifer VillaseñorDiane Mathis
Dec 6, 2008·Genes & Development·Fatih OzsolakDavid E Fisher
Mar 24, 2009·Annual Review of Immunology·Diane Mathis, Christophe Benoist
May 26, 2009·Immunity·Liang ZhouDan R Littman
Jul 16, 2009·Nature Reviews. Molecular Cell Biology·Myriam HembergerWolf Reik
Aug 15, 2009·The EMBO Journal·Yong FanMassimo Trucco
Jan 16, 2010·RNA·Alex Mas MonteysBeverly L Davidson
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Rosa KarlićMartin Vingron
Oct 23, 2010·Proceedings of the National Academy of Sciences of the United States of America·Lars-Oliver TykocinskiBruno Kyewski
Feb 24, 2011·Current Opinion in Genetics & Development·Guohong Li, Danny Reinberg
Apr 21, 2011·Nature Communications·María MittelbrunnFrancisco Sánchez-Madrid
May 18, 2011·Genes & Development·Aimée M Deaton, Adrian Bird
Jun 28, 2011·Nature Cell Biology·Daan NoordermeerWouter de Laat
Aug 23, 2011·Nature Genetics·Shankar MukherjiAlexander van Oudenaarden
Dec 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Matthieu GiraudChristophe Benoist
May 1, 2012·Stem Cells and Development·Gu BinZhang Ming
Jan 1, 2011·Frontiers in Immunology·Dina Danso-AbeamAdrian Liston
Jul 31, 2012·Molecular Cell·Christoph BockAlexander Meissner
Sep 14, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Saulius ZuklysGeorg A Holländer
Dec 6, 2012·Nature Structural & Molecular Biology·Catherine A MusselmanTatiana G Kutateladze

❮ Previous
Next ❯

Citations

Jan 19, 2016·Journal of Autoimmunity·José Ignacio SaldañaTessa Crompton
Dec 24, 2015·Frontiers in Immunology·Geraldo Aleixo PassosErnna Hérida Oliveira
Dec 5, 2015·Frontiers in Immunology·Wilson SavinoVinicius Cotta-de-Almeida
Aug 11, 2015·Frontiers in Immunology·Gabriel SkogbergOlov Ekwall
Nov 9, 2016·Scientific Reports·Vanja LundbergOlov Ekwall
Mar 7, 2017·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Xu ZhangHai-Feng Li
Jan 17, 2017·Journal of Immunotoxicology·Martha Ustarroz-CanoTeresa I Fortoul
Sep 6, 2017·Immunology·Geraldo A PassosDaniella A Mendes-da-Cruz
Jun 6, 2018·Frontiers in Immunology·Cesar A Speck-HernandezGeraldo A Passos
Apr 30, 2020·Genome Medicine·Jean-David LaroucheClaude Perreault
Feb 28, 2018·Frontiers in Immunology·Roberto Perniola
Jun 18, 2020·Frontiers in Immunology·Ernna H OliveiraGeraldo A Passos
Apr 20, 2021·Trends in Genetics : TIG·Pierre PontarottiJulien Paganini

❮ Previous
Next ❯

Methods Mentioned

BETA
acetylation

Software Mentioned

pGE

Related Concepts

Related Feeds

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.