|Nuclear Cell Biology - CNRS URA2582|
|HEAD||Dr GALY Vincent / firstname.lastname@example.org|
|MEMBERS||Dr BACHELLIER-BASSI Sophie / BERGER Axel / CABAL Ghislain / Dr DAVID-WATINE Brigitte
Dr FEUERBACH Frank / Dr MHLANGA Musa / Dr NEHRBASS Ulf
We are studying nuclear structure / function relationships and thereby focus on characterizing the regulatory function and molecular determinants of gene positioning within the nuclear space. Biological and informatic tools co-developed in our laboratory allow for the accurate measurement of single and multiple gene loci positions in living yeast cells under inactive and active conditions. Further, we have started to study nuclear architecture-linked gene regulation during differentiation and developmental processes in nematodes.
1. Role of transcription and export machineries in spatial positioning of transcribed genes
In several cellular systems, transcriptional states may be linked to specific sub-nuclear compartments. While, in S. cerevisiae, domains close to the nuclear periphery are implicated in transcriptional silencing, it has been proposed that distinct gene loci move to the nuclear envelope (NE) during gene expression. We therefore analyzed spatial positioning of the GAL genes that are activated by the SAGA complex in response to nutritional change. In collaboration with the Quantitative Image Analyses laboratory (LAIQ) we developed an application for automatic detection and localization of single fluorescently tagged loci in 3D+time and observed that, upon induction, the GAL locus is confined close to the NE. By simultaneous detection of GAL transcripts we showed that transcription occurs preferentially while genes motility is being confined close to the NE. Further, we found that spatial positioning of active genes was conferred by the transcriptionally activating factors of the SAGA complex, in conjunction with NPC components. Accordingly, cells can use this so called ‘gene gating’, to encode transcriptional regulation within spatial gene positioning and nuclear architecture.
2. Role of the nucleolus on nuclear organization
In order to analyse how genes that need to be co-regulated for ribosome biogenesis are positioned within the nuclear volume, we - in collaboration with LAIQ - extended the gene localization method by introducing a second nuclear landmark different from the NE. Labelling the nucleolus allowed both to analyse gene position with respect to this major sub-nuclear compartment and to orient the imaged nuclei. Since, gene position information of aligned nuclei can be merged, we have for the first time access to statistical robust high precision localization probability maps.
3. Structural and functional nuclear organization in metazoan
In parallel of our analysis in yeast, we analyzed the structure/function relationships in metazoans using human cells in culture as well as C. elegans and D. melanogaster embryos. We started the analysis of several NE components, including the orthologs of the Mlp proteins in these organisms and are currently analyzing their function in the cell as well as at the organism level.
|Publications 2006 of the unit on Pasteur's references database|
Activity Reports 2006 - Institut Pasteur
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