Dynamics of chromatin structure and transcription regulation
Over the past years our lab has identified and characterized a large number of metazoan nuclear transcription factors. These regulatory proteins include RNA polymerase II initiation factors and co-activators that often form large multi-subunit complexes at promoter DNA to mediate transcription initiation and/or modify the epigenetic landscape of the genome. Our studies demonstrate that large co-activator complexes play a critical role in mediating general and cell type specific transcription as well as chromatin-regulatory processes. Our main research interest is to study the nature of the molecular machineries and mechanisms that control how specific protein coding genes are turned on and off in the nucleus of a given cell, during growth, differentiation and development, and how does disruption of this highly regulated process lead to various disease states We use biochemical, genetic, cell biology, imaging and structural approaches to study the control of gene expression, genome stability and chromatin architecture in different eukaryotic organisms (yeast, mouse and human). Our current and planned activities aim to better understand regulatory processes in different cellular systems under physiological conditions and also during the development of intact vertebrate organisms.
1. Study of TFIID and different chromatin modifying complexes during differentiation and development
2. Study the assembly and dynamic action of transcription complexes in regulation of gene expression
3. Study the regulation of histone H2B monoubiquitination and its role in cellular homeostasis
4. Study the role of mRNA export complex in chromatin architecture and genome stability
Using a combination of fluorescence microscopy, antibody labelling, GFP (green fluorescent protein) tracking, ChIP (chromatin immunoprecipitation), single molecule RNA FISH (fluorescence in situ hybridization), we have started to analyse the mechanisms that regulate transcription at a higher resolution. Furthermore, to answer our questions, we use a wide combination of biochemistry based assays: protein immunoprecipitation coupled with mass spectrometry assays, genome-wide gene expression studies (RNA-seq) and transcription factor occupancy studies (ChIP-seq), 4-TU based nascent transcript measurements, but also yeast and mouse genetics and several other imaging techniques (FRAP, FCS, STED, 3D-SIM, spt-PALM).
- Dr. Marc H.T.M. Timmers, Utrecht University, Utrecht, The Netherlands, TAF-TFIID project
- Dr. Iannis Talianidis, BIOMEDICAL SCIENCES RESEARCH CENTER, Alexander Fleming, Athens, Greece, TFIID project
- Dr. Ferenc Müller, Department of Medical and Molecular Genetics, School of Clinical and Experimental Medicine, University of Birmingham; UK, TAF-TBP like project,
- Dr. Sophia Georgieva, Institute of Gene Biology, Moscow, Russia, mRNA export project
- Dr. Cheng-Fu Kao, Academia Sinica, Taipei, Taiwan, International common ANR project histone H2B deubiquitination
- Dr. Graham Wright, Institute of Medical Biology, Singapore, Super resolution imaging, TFIID, SAGA and ATAC project
- Drs. Yves Mely and Pascal Didier, UdS, Laboratoire Biophotonique et des interactions moleculaires, Illkirch, France, Super resolution imaging, TFIID, SAGA and ATAC project
- Dr. Etienne Weiss, ESBS UdS, Illkirch, France, Dynamic visualization of nuclear transcription factors
- Dr. Robert Schneider, IGBMC, Illkirch, France, analyzing novel acetylation sites in the chromatin
- Dr. Patrick Schultz; IGBMC, Illkirch, France, EM structure of TFIID and ATAC complexes
- Dr. Imre Berger, EMBL, Grenoble, structure of TFIID and ATAC complexes
- Laszlo TORA - ERC Advanced Grant - European Research Council - 2013
- Laszlo TORA - Etancelin Grand Prize - Institut de France de l'Académie des Sciences - 2011
- Laszlo TORA - Scientific Prize - Helmholtz Humboldt Research - 2005
- Laszlo TORA - Member of the European Molecular Biology Organization (EMBO) - European Molecular Biology Organization (EMBO) - 2001
- Laszlo TORA - Silver Medal - CNRS - 2001
- April 25, 2016 - IGBMC Researchers once again distinguished by the European Research Council
- Jan. 14, 2015 - Discovery of a stage of formation in the cytoplasm for the TFIID transcription factor
- Sept. 15, 2014 - SAGA: an underestimated role in the transcription of our genes
- Dec. 1, 2013 - László Tora, winner of the 2013 ERC Advanced Grant
- Jan. 6, 2013 - At the heart of transcription
- April 15, 2012 - New roles of Histone H1 in transcription
- Dec. 23, 2011 - New light shed on chromosome fragility
- Aug. 1, 2010 - H3.3, a histone at the origin of development
Exp Cell Res March 8, 2016 ; 342:145-158 .
Elife Feb. 25, 2016 ; 5:E12534 .
Systems Biology of Cancer avr 2015 2015 ; PT 2:56-69 .
PLoS One Nov. 10, 2015 ; 10:e0142226 .
J Biol Chem Nov. 27, 2015 ; 290:28997-9009 .
Mol Cell Biol June 15, 2015 ; 35:2103-18 .
Nat Commun Jan. 14, 2015 ; 6:6011 .
PLoS Genet Oct. 2, 2014 ; 10:e1004667 .
Structure Oct. 16, 2014 ; 22:1553-1559 .
Genes Dev Sept. 15, 2014 ; 28:1999-2012 .