RNA interference machinery influences the nuclear organization of a chromatin insulator

• Published in: Nature genetics Vol. 38; no. 8; pp. 936 - 941
• Main Authors: Lei, Elissa P, Corces, Victor G
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.08.2006; Nature Publishing Group
• Subjects: Agriculture; Animal Genetics and Genomics; Animals; Binding sites; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell Nucleus - genetics; Chromatin; Chromatin - genetics; Chromatin. Chromosome; Deoxyribonucleic acid; DNA; Drosophila melanogaster; Drosophila melanogaster - genetics; Female; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Function; Gene mutations; Genes, Insect; Genetic aspects; Genetics of eukaryotes. Biological and molecular evolution; Health aspects; Human Genetics; Insulator Elements; letter; Models, Genetic; Molecular and cellular biology; Molecular genetics; Mutation; Physiological aspects; Recombinant Proteins - genetics; Ribonucleic acid; RNA; RNA Interference; Transcription Factors - genetics; United States; Gene silencing; Chromosome; Chromatin; RNA interference
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng1850

RNA interference (RNAi) is a conserved silencing mechanism that can act through alteration of chromatin structure. Chromatin insulators promote higher-order nuclear organization, thereby establishing DNA domains subject to distinct transcriptional controls. We present evidence for a functional relationship between RNAi and the gypsy insulator of D. melanogaster . Insulator activity is decreased when Argonaute genes required for RNAi are mutated, and insulator function is improved when the levels of the Rm62 helicase, involved in double-stranded RNA (dsRNA)-mediated silencing and heterochromatin formation, are reduced. Rm62 interacts physically with the DNA-binding insulator protein CP190 in an RNA-dependent manner. Finally, reduction of Rm62 levels results in marked nuclear reorganization of a compromised insulator. These results suggest that the RNAi machinery acts as a modulator of nuclear architecture capable of effecting global changes in gene expression.