Mdig de-represses H19 large intergenic non-coding RNA (lincRNA) by down-regulating H3K9me3 and heterochromatin

Citations Over TimeTop 10% of 2013 papers

Abstract

Mineral dust-induced gene (mdig) had been linked to the development of human lung cancers associated with environmental exposure to mineral dust, tobacco smoke or other carcinogens. In the present studies, we demonstrated that the overexpression of mdig in A549 adenocarcinomic human alveolar type II epithelial cells decreases the heterochromatin conformation of the cells and de-represses the transcription of genes in the tandemly repeated DNA regions. Although mdig can only cause a marginal decrease of the total histone H3 lysine 9 trimethylation (H3K9me3), a significant reduction of H3K9me3 in the promoter region of H19, the paternally imprinted but maternally expressed gene transcribing a large intergenic non-coding RNA (lincRNA), was observed in the cells with mdig overexpression. Silencing mdig by either shRNA or siRNA not only increased the level of H3K9me3 in the promoter region of H19 but also attenuated the transcription of H19 long non-coding RNA. Demethylation assays using immunoprecipitated mdig and histone H3 peptide substrate suggested that mdig is able to remove the methyl groups from H3K9me3. Clinically, we found that higher levels of mdig and H19 expression correlate with poorer survival of the lung cancer patients. Taken together, our results imply that mdig is involved in the regulation of H3K9me3 to influence the heterochromatin structure of the genome and the expression of genes important for cell growth or transformation.

Related Papers

• → Arabidopsis REF6 is a histone H3 lysine 27 demethylase(2011)411 cited
• → UTX, a Histone H3-Lysine 27 Demethylase, Acts as a Critical Switch to Activate the Cardiac Developmental Program(2011)253 cited
• → The Histone H3 Lysine 27-Specific Demethylase Jmjd3 Is Required for Neural Commitment(2008)205 cited
• → Epigenetic modifications control the phenotype of alternatively activated macrophages (136.4)(2009)
• → Faculty Opinions recommendation of Arabidopsis REF6 is a histone H3 lysine 27 demethylase.(2011)