RESUMO
Long intergenic noncoding RNAs (lincRNAs) can regulate the transcription of inflammatory genes and thus may represent a new group of inflammatory mediators with a potential pathogenic role in inflammatory diseases. Here, our genome-wide transcriptomic data show that TNF-α stimulation caused up-regulation of 171 lincRNAs and down-regulation of 196 lincRNAs in murine intestinal epithelial cells in culture. One of the up-regulated lincRNAs, lincRNA-Cox2, is an early-responsive lincRNA induced by TNF-α through activation of the NF-ĸB signaling pathway. Knockdown of lincRNA-Cox2 resulted in reprogramming of the gene expression profile in intestinal epithelial cells in response to TNF-α stimulation. Specifically, lincRNA-Cox2 silencing significantly (P < 0.05) enhanced the transcription of Il12b, a secondary late-responsive gene induced by TNF-α. Mechanistically, lincRNA-Cox2 promoted the recruitment of the Mi-2/nucleosome remodeling and deacetylase (Mi-2/NuRD) repressor complex to the Il12b promoter region. Recruitment of the Mi-2/NuRD complex was associated with decreased H3K27 acetylation and increased H3K27 dimethylation at the Il12b promoter region, which might contribute to Il12b trans-suppression by lincRNA-Cox2. Thus, our data demonstrate a novel mechanism of epigenetic modulation by lincRNA-Cox2 on Il12b transcription, supporting an important role for lincRNAs in the regulation of intestinal epithelial inflammatory responses.
Assuntos
Interleucina-12/genética , Complexo Mi-2 de Remodelação de Nucleossomo e Desacetilase/metabolismo , RNA Longo não Codificante/genética , Fator de Necrose Tumoral alfa/metabolismo , Acetilação , Animais , Linhagem Celular , Ciclo-Oxigenase 2/metabolismo , Regulação para Baixo , Epigenômica/métodos , Células Epiteliais/metabolismo , Histonas/genética , Interleucina-12/metabolismo , Mucosa Intestinal/metabolismo , Complexo Mi-2 de Remodelação de Nucleossomo e Desacetilase/genética , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Nucleossomos/genética , Regiões Promotoras Genéticas , RNA Longo não Codificante/metabolismo , Transcrição Gênica , Ativação Transcricional , Fator de Necrose Tumoral alfa/genética , Regulação para CimaRESUMO
Artemia diapause has been extensively studied in embryonic biology for a long time. It has been demonstrated that hydrogen peroxide (H2O2) can increase the hatching rate in the development and diapause termination of Artemia cysts. This study used an untargeted 1H NMR-based metabolomic approach to explore the physiological regulation of H2O2 in initiating the development and terminating the diapause of Artemia cysts. This experiment was divided into two parts. In the first part, we analyzed three groups with or without H2O2 as control-0h, control-5h and H2O2 (180µM)-5h; in the second part, after 7-d incubation, the non-hatching cysts were treated with different H2O2 concentrations as low as 180µM and as high 1800µM. The results showed that arginine and proline metabolism were up-regulated after 5h, and H2O2 up-regulated valine, leucine and isoleucine biosynthesis in the development of cysts. In the second part, low H2O2 (180µM) showed alanine, aspartate and glutamate metabolism, but high H2O2 (1800µM) also up-regulated arginine and proline metabolism, as in the control group without H2O2 stimulus. These results suggest that enough H2O2 can catalyze cell transcription and translation in Artemia cysts, and it improves the cell growth rate, thus allowing embryo cells to grow again.