TY - JOUR
T1 - SAGA interacting factors confine sub-diffusion of transcribed genes to the nuclear envelope
AU - Cabal, Ghislain G.
AU - Genovesio, Auguste
AU - Rodriguez-Navarro, Susana
AU - Zimmer, Christophe
AU - Gadal, Olivier
AU - Lesne, Annick
AU - Buc, Henri
AU - Feuerbach-Fournier, Frank
AU - Olivo-Marin, Jean Christophe
AU - Hurt, Eduard C.
AU - Nehrbass, Ulf
N1 - Funding Information:
Acknowledgements 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T. Fischer and all the members of the Nehrbass group for critical discussions, and A. Taddei and S. Gasser for sharing unpublished results.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 Franc¸ais délégué à la Recherche et aux Nouvelles Technologies.
PY - 2006/6/8
Y1 - 2006/6/8
N2 - Changes in the transcriptional state of genes have been correlated with their repositioning within the nuclear space. Tethering reporter genes to the nuclear envelope alone can impose repression and recent reports have shown that, after activation, certain genes can also be found closer to the nuclear periphery. 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' hypothesis.
AB - Changes in the transcriptional state of genes have been correlated with their repositioning within the nuclear space. Tethering reporter genes to the nuclear envelope alone can impose repression and recent reports have shown that, after activation, certain genes can also be found closer to the nuclear periphery. 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' hypothesis.
UR - http://www.scopus.com/inward/record.url?scp=33745001795&partnerID=8YFLogxK
U2 - 10.1038/nature04752
DO - 10.1038/nature04752
M3 - Article
C2 - 16760982
AN - SCOPUS:33745001795
SN - 0028-0836
VL - 441
SP - 770
EP - 773
JO - Nature
JF - Nature
IS - 7094
ER -