EZH2 and histone 3 trimethyl lysine 27 associated with Il4 and Il13 gene silencing in Th1 cells.
Differentiation of naïve CD4 T cells toward the T helper 1 (T(H)1) and T helper 2 (T(H)2) fates involves the transcriptional repression and enhancement, respectively, of Il4 and Il13, adjacent chromosome 11 genes encoding the canonical T(H)2 cytokines interleukin-4 and interleukin-13. Proper execution of this developmental fate choice during immune responses is critical to host defense and, when misregulated, leads to susceptibility to infectious microbes and to allergic and autoimmune diseases. Here, using chromatin immunoprecipitation and real time reverse transcription PCR we identify the Polycomb family histone methyltransferase EZH2 as the enzyme responsible for methylating lysine 27 of histone H3 at the Il4-Il13 locus of T(H)1 but not T(H)2 cells, implicating EZH2 in the mechanism of Il4 and Il13 transcriptional silencing.
Koyanagi
Madoka
M
Department of Immunology, University of Washington, Seattle, Washington 98195-7650, USA.
Baguet
Aurelie
A
Martens
Joost
J
Margueron
Raphael
R
Jenuwein
Thomas
T
Bix
Mark
M
D000818:Animals; D000071221:Enhancer of Zeste Homolog 2 Protein; D020868:Gene Silencing / Q000276:immunology*; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000502:physiology*; D006657:Histones / Q000276:immunology / Q000502:physiology; D018793:Interleukin-13 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D008239:Lysine / Q000031:analogs & derivatives / Q000235:genetics / Q000502:physiology; D008780:Methyltransferases / Q000235:genetics / Q000502:physiology*; D051379:Mice; D041681:NIH 3T3 Cells; D063151:Polycomb Repressive Complex 2; D063146:Polycomb-Group Proteins; D011496:Protein Methyltransferases; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology; D018417:Th1 Cells / Q000201:enzymology / Q000502:physiology*; D018418:Th2 Cells / Q000502:physiology
D006657:Histones; D018793:Interleukin-13; D063146:Polycomb-Group Proteins; D011506:Proteins; D012097:Repressor Proteins; D015847:Interleukin-4; C481527:Dot1l protein, mouse; D000076983:Histone Methyltransferases; D008780:Methyltransferases; D011496:Protein Methyltransferases; D000071221:Enhancer of Zeste Homolog 2 Protein; C498410:Ezh2 protein, mouse; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2; D008239:Lysine