5-Azacytidine suppresses RNA polymerase II recruitment to the SLPI gene.
Histone methylation is regarded as a stable modification important in the epigenetic regulation of gene expression. Transcriptionally active chromatin is methylated at H3-K4 whereas repressed chromatin is methylated at H3-K9. To investigate the role of histone methylation in an acute inflammatory response, A549 cells were treated with IL-1beta and/or the methylase inhibitor 5-azacytidine (5-aza), and histone H3-K4 methylation levels and transcription of secretory leukocyte protease inhibitor (SLPI) were measured. IL-1beta stimulation enhanced histone H3-K4 tri-methylation across the SLPI coding region at 24h. In parallel, IL-1beta enhanced recruitment of RNA polymerase II to the SLPI gene. 5-aza attenuated both H3-K4 tri-methylation and RNA polymerase II recruitment to a similar extent resulting in reduced SLPI mRNA and protein levels. These data suggest that in addition to epigenetic regulation of constitutive SLPI expression, H3-K4 tri-methylation may play a role in stimulated SLPI expression by modulating RNA polymerase II recruitment and subsequent gene transcription.
Wada
Hiroo
H
Airway Disease Section, National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK.
Kagoshima
Masahiko
M
Ito
Kazuhiro
K
Barnes
Peter J
PJ
Adcock
Ian M
IM
D000818:Animals; D001374:Azacitidine / Q000494:pharmacology*; D002460:Cell Line; D019175:DNA Methylation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000037:antagonists & inhibitors*; D006657:Histones / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology; D008745:Methylation / Q000187:drug effects; D011496:Protein Methyltransferases; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000235:genetics*; D012319:RNA Polymerase II / Q000037:antagonists & inhibitors*; D014158:Transcription, Genetic / Q000187:drug effects
D004791:Enzyme Inhibitors; D006657:Histones; D007375:Interleukin-1; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000076983:Histone Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D012319:RNA Polymerase II; D001374:Azacitidine