Jakociunas, Tadas4; Domange Jordö, Marie Elise4; Mebarek, Mazhoura Aït3; Bünner, Camilla Marie3; Hansen, Janne Verhein4; Oddershede, Lene Broeng5; Thon, Genevieve4
1 Functional Genomics, Department of Biology, Faculty of Science, Københavns Universitet2 Biocomplexity, The Niels Bohr Institute, Faculty of Science, Københavns Universitet3 Biologisk Institut, Københavns Universitet4 Functional Genomics, Department of Biology, Faculty of Science, Københavns Universitet5 Biocomplexity, The Niels Bohr Institute, Faculty of Science, Københavns Universitet
Our research addresses the relationship between subnuclear localization and gene expression in fission yeast. We observed the relocalization of a heterochromatic region, the mating-type region, from its natural location at the spindle-pole body to the immediate vicinity of the nucleolus. Relocalization occurred in response to a DNA rearrangement replacing a boundary element (IR-R) with a ribosomal DNA repeat (rDNA-R). Gene expression was strongly silenced in the relocalized mating-type region through mechanisms that differ from those operating in wild type. Also different from the wild-type situation, programmed recombination events failed to take place in the rDNA-R mutant. Increased silencing and perinucleolar localization depended on Reb1, a DNA-binding protein with cognate sites in the rDNA. Reb1 was recently shown to mediate long-range interchromosomal interactions in the nucleus through dimerization, providing a mechanism for the observed relocalization. Replacing the full rDNA repeat with Reb1-binding sites, and using mutants lacking the histone H3K9 methyltransferase Clr4, indicated that the relocalized region was silenced redundantly by heterochromatin and another mechanism, plausibly antisense transcription, achieving a high degree of repression in the rDNA-R strain.
National Academy of Sciences. Proceedings, 2013, Vol 110, Issue 47