On the mechanism of induction of heterochromatin by the RNA-binding protein vigilin.
Vigilin is an RNA-binding protein localized to both the cytoplasm and the nucleus and has been previously implicated in heterochromatin formation and chromosome segregation. We demonstrate here that the C-terminal domain of human vigilin binds to the histone methyltransferase SUV39H1 in vivo. This association is independent of RNA and maps to a site on vigilin that is not involved in its interaction with several other known protein partners. Cells that express high levels of the C-terminal fragment display chromosome segregation defects, and ChIP analyses show changes in the status of pericentric beta-satellite and rDNA chromatin from heterochromatic to more euchromatic form. Finally, a cell line with inducible expression of the vigilin C-terminal fragment displays inducible alterations in beta-satellite chromatin. These and other results lead us to present a new model for vigilin-mediated, RNA-induced gene silencing.
Zhou
Jing
J
Department of Genetics and Developmental Biology, University of Connecticut Stem Cell Institute, University of Connecticut Health Center, Farmington, Connecticut 06030-3301, USA
Wang
Qiaoqiao
Q
Chen
Ling-Ling
LL
Carmichael
Gordon G
GG
D034961:Antigens, Nuclear / Q000378:metabolism; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D020090:Chromosome Segregation / Q000235:genetics; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D020868:Gene Silencing; D006570:Heterochromatin / Q000378:metabolism*; D006801:Humans; D000072200:Ku Autoantigen; D008780:Methyltransferases / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D006570:Heterochromatin; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; C075197:high density lipoprotein binding protein; D012313:RNA; C407843:SUV39H1 protein, human; D008780:Methyltransferases; C098487:DHX9 protein, human; C000606509:Xrcc6 protein, human; D053487:DEAD-box RNA Helicases; D000072200:Ku Autoantigen