Changes in the transcriptional state of genes have been correlated with their repositioning within the nuclear space1. Tethering reporter genes to the nuclear envelope alone can impose repression2 and recent reports have shown that, after activation, certain genes can also be found closer to the nuclear periphery3,4,5,6. The molecular mechanisms underlying these phenomena have remained elusive. Here, with the use of dynamic three-dimensional tracking of a single locus in live yeast (Saccharomyces cerevisiae) cells, we show that the activation of GAL genes (GAL7, GAL10 and GAL1) leads to a confinement in dynamic motility. We demonstrate that the GAL locus is subject to sub-diffusive movement, which after activation can become constrained to a two-dimensional sliding motion along the nuclear envelope. RNA-fluorescence in situ hybridization analysis after activation reveals a higher transcriptional activity for the peripherally constrained GAL genes than for loci remaining intranuclear. This confinement was mediated by Sus1 and Ada2, members of the SAGA histone acetyltransferase complex, and Sac3, a messenger RNA export factor, physically linking the activated GAL genes to the nuclear-pore-complex component Nup1. Deleting ADA2 or NUP1 abrogates perinuclear GAL confinement without affecting GAL1 transcription. Accordingly, transcriptional activation is necessary but not sufficient for the confinement of GAL genes at the nuclear periphery. The observed real-time dynamic mooring of active GAL genes to the inner side of the nuclear pore complex is in accordance with the ‘gene gating’ hypothesis7.
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We thank D. Fagegaltier, E. Fabre, P. Therizol, B. Zhang, T. Fischer and all the members of the Nehrbass group for critical discussions, and A. Taddei and S. Gasser for sharing unpublished results. We thank the ‘Plateforme d'imagerie dynamique’ of the Pasteur Institute for providing access to the microscopy facilities. This work was supported by an ACI-BCMS grant. G.G.C. and A.G. were recipients of fellowships of the Ministère Français délégué à la Recherche et aux Nouvelles Technologies. Author Contributions E.C.H. and U.N. conceived the project. G.G.C. did the experiments. S.R.-N. did the RT–PCR experiment. G.G.C. and O.G. conceived the image analysis protocols. A.G. and J.-C.O.-M. conceived the image analysis algorithms in collaboration with G.G.C. and O.G. A.G. implemented the image analysis algorithms. G.G.C. did the image processing and analysis. G.G.C. and C.Z. computed the MSD. G.G.C., O.G., C.Z., H.B. and A.L. interpreted the image analysis results. G.G.C., S.R.-N. and F.F.-F. provided the yeast strains and plasmid constructs. U.N. wrote the paper. F.F.-F. supervised G.G.C. J.-C.O.-M. supervised A.G. J.-C.O.-M., E.C.H. and U.N. are head of the laboratories participating in this work.
About this article
Nature Reviews Molecular Cell Biology (2016)