Source: Annual Congress 2003 - Molecular biology of chronic lung disease and lung cancer
Disease area: Airway diseases

Abstract

Tightly compacted within the nucleus, DNA is inaccessible to transcription factors and RNA polymerase II. The histone code proposes that gene transcription occurs as a result of post-translational changes in histones. Methylation of histone H3 residues Lys(K)4 and K9, particularly their di- or tri-methylated status, have been reported to be involved in the activation and the suppression of the transcription. In addition, we have previously reported that 5-aza cytidine (5-aza), a methylase inhibitor, enhanced IL-1β stimulated GM-CSF release and synergised with TSA, a deacetylase inhibitor, to block dexamethasone-induced suppression. We thus hypothesised that histone H3 K4/K9 methylation was involved in the regulation of inflammatory genes. A549 cells were incubated with dexamethasone (Dex, 10^-12-10^-6M) and/or IL-1β (1 ng/ml) for 0, 1, 4, 24hr and histone H3 K4/K9 tri-/dimethylation was measured by Western blotting. Both Dex and IL-1β induced a reduction in K9 di-methylation at 4hr followed by a significant induction at 24hr. Dex was able to attenuate the effect of IL-1β on K9 dimethylation at 4hr. Histone H3K4 dimethylation did not change demonstrably over 24 hr. Chromatin immunoprecipitation assays showed that K9 methylation at the NF-kB site in the GM-CSF promoter was enhanced by both IL-1β and Dex within 1hr. In combination with Real Time PCR, it also showed K9 methylation at the NF-kB site in the SLPI promoter was enhanced by IL-1β and Dex either alone or in combination at 24hr. This data suggests that histone H3 methylation may play a role in inflammatory gene expression induced by IL-1β.

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Citations should be made in the following way:
H. Wada, M. Kagoshima, P. J. Barnes, I. M. Adcock (London, United Kingdom). The effects of dexamethasone and IL-1β on histone H3 methylation in A549 cells. Eur Respir J 2003; 22: Suppl. 45, 1503

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