Abstract IA5: Epigenetic genome control by heterochromatin machinery and non-coding RNAs

Abstract

Abstract Heterochromatin assembly involving posttranslational modifications of histones is critical for various chromosomal processes including the regulation of gene expression and the maintenance of genomic integrity. Defective heterochromatin formation has been linked to cancer. Our previous work has shown that non-coding RNAs and the RNAi machinery, involved in the processing of non-coding RNAs, play prominent roles in the assembly of heterochromatin structures. Indeed, the loss of factors involved in RNAi such as Argonaute, Dicer and RNA-dependent RNA polymerase cause severe defects in centromeric heterochromatin formation, leading to missegregation of chromosomes during cell division. An Argonaute-containing RNAi effector complex named RITS has been identified that facilitates the loading of a conserved histone methyltransferase Clr4/Suv39h, which is essential for heterochromatin assembly. We have recently discovered an unexpected role for heterochromatin factors in the RNA quality control. Heterochromatin factors localize broadly across the genome and collaborate with RNAi machinery to suppress potentially deleterious RNAs, the uncontrolled accumulation of which can cause DNA damage and modify epigenetic genomic profiles. I will present our recent findings showing that non-coding RNAs and heterochromatin play important roles in dynamic regulation of genomes, which has important implications for human health and disease. Citation Format: Shiv Grewal. Epigenetic genome control by heterochromatin machinery and non-coding RNAs [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr IA5.