Long non-coding RNAs and their implications in cancer epigenetics

LncRNAs (long non-coding RNAs) have emerged as key molecular players in the regulation of gene expression in different biological processes. Their involvement in epigenetic processes includes the recruitment of histone-modifying enzymes and DNA methyltransferases, leading to the establishment of chromatin conformation patterns that ultimately result in the fine control of genes. Some of these genes are related to tumorigenesis and it is well documented that the misregulation of epigenetic marks leads to cancer. In this review, we highlight how some of the lncRNAs implicated in cancer are involved in the epigenetic control of gene expression. While very few lncRNAs have already been identified as players in determining the cancer-survival outcome in a number of different cancer types, for most of the lncRNAs associated with epigenetic regulation only their altered pattern of expression in cancer is demonstrated. Thanks to their tissue-specificity features, lncRNAs have already been proposed as diagnostic markers in specific cancer types. We envision the discovery of a wealth of novel spliced and unspliced intronic lncRNAs involved in epigenetic networks or in highly location-specific epigenetic control, which might be predominantly altered in specific cancer subtypes. We expect that the characterization of new lncRNA (long non-coding RNA)–protein and lncRNA–DNA interactions will contribute to the discovery of potential lncRNA targets for use in therapies against cancer.     

Positive and negative regulation ofCAR1 Expression inSaccharomyces cerevisiae

Summary We localized the chromosomal targets of several of the regulatory controls of expression of theCAR1 gene. Fusion tolacZ of several fragments of the 5′ non-coding region showed that induction ofCAR1 by arginine is positively regulated by the products of theARGR genes. The target lies upstream of another site where repression by the CARGRI molecule occurs. The latter control is not specific to arginine catabolism since it also affectsCYC-1 and indeed does not appear to involve arginine. The primary target of the two other regulatory allelesCARGRII andCARGRIII is not situated in the 5′ non-coding region. Deletion analysis supports the fusion data and confirms the order of the regulatory regions: 5′—nitrogen catabolite repression—activation by arginine—CARGRI-mediated repression—CAR1.