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Transcription complexes variability in development and disease

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Transcription complexes variability in development and disease

DEPARTMENT

Functional genomics and cancer

TEAM LEADER

Stephane VINCENT

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 (TFIID in particular) and co-activators (Spt-Ada-Gcn5 acetyl transferase, SAGA; or Ada Two A containing; ATAC) that 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 these complexes or their variants play a critical role in regulating transcription, as well as chromatin-regulatory processes. Our main research interest is to study the nature and assembly of these molecular machineries, the mechanisms by which they control how specific protein coding genes are turned on and off in the nucleus of a given cell, during growth, differentiation and development. We use biochemical, genetic, cell biology, imaging, biophysical, bioinformatic 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 gene regulatory processes in different cellular systems and during the development of intact vertebrate organisms. We are also interested how does the disruption of this highly regulated processes lead to various disease states.

Research subgroup(s)

Current projects

1) Study the assembly of transcription complexes;

2) Analysis of preinitiation complex variability and their role in transcription regulation during development and differentiation (during oocyte growth in particular);

        

3) Understanding the role of co-activator complexes in transcription regulation;

 

4) Investigation of of general transcription factor behavior, recruitment and RNA polymerase II transcription in living cells at transcribed genes;

 

5) Characterize how and why TAF mutations cause neuronal disorders and intellectual disabilities?

 

 

 

Collaborations and networks

  • Dr. Marc H.T.M. Timmers, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Medical Center-University of Freiburg, Germany, ANR-PRCI project

  • Dr. Dominique Helmlinger, Centre de Recherche en Biologie Cellulaire de Montpellier (CRBM), CNRS UMR5237, Montpellier, France; and Nacho Molina, ANR project;
  • Dr. Fred Coin, IGBMC; IGBMC, Illkirch, France, ANR project
  • Prof. Ferenc Müller, Department of Medical and Molecular Genetics, School of Clinical and Experimental Medicine, University of Birmingham; UK, TBPL2 project,
  • Prof. Imre Berger, Bristol University, TBPL2 project,
  • Prof. Boris Lenhard, Imperial College London, UK; TBPL2 project,
  • Dr. Iannis Talianidis, Institute of Molecular Biology & Biotechnology, FORTH, Herakleion, Crete, Greece, EU-ITN project;
  • Dr. Pascal Didier, UdS, Laboratoire Biophotonique et des interactions moleculaires, Illkirch, France, Imaging project;
  • Dr. Nacho Molina, IGBMC, Illkirch, France, Quantification and analysis of nuclear transcription factor behavior and recruitment project
  • Dr Bertrand Séraphin, IGBMC, Illkirch, analysis of regulation of mRNA decay during oocyte growth;
  • Prof. Stéphane Viville, Hôpital Universitaire de Strasbourg, identification of TBPL2 mutations associated with female infertility in patients, FRM project;
  • Prof. Etienne Weiss, ESBS UdS, Illkirch, France, Visualization of nuclear transcription factors project;
  • Dr. Patrick Schultz and Dr. Gabor Papai; IGBMC, Illkirch, France, cryo-EM structure of TFIID, SAGA and ATAC complexes;
  • Dr. Florian Müller, Pasteur Institute, Paris, France, TFIID assembly project;
  • Prof. Michael Poirier, Ohio State University (OSU), Ohio, USA; NIH RO1 grant, characterization of HAT complexes
  • Prof. Carlos Castro, Department of Mechanical and Aerospace Engineering, OSU, USA; NSF grant, DNA origami project.
  • Dr. Melike Lakadamyali, University of Pennsylvania, Perelman School of Medicine, Department of Physiology, Philadelphia, USA, NSF grant, DNA origami project.
  • Prof. Jeff Ranish, Institute for Systems Biology, Seattle, USA; Crosslinked mass spec projects on TFIID, SAGA and ATAC.
  • Prof. Steve Hahn, Fred Hutchinson Cancer Research Center, Seattle, USA; the role of SAGA and TFIID in yeast.

Funding and partners

Research Support for the Tora team in the past 10 years

  • INCa PLBIO24-261, project: Understanding the biology and drug resistance of CDX2/UBTF B-cell acute lymphoblastic leukaemia (S.D. Vincent partner)
  • ANR PRC Programme 2023 (ANR-23-CE12-0034-01), project: Biological significance of the specific transcription machinery during oocyte growth (S.D. Vincent coordinator)
  • ANR PRCI Programme 2023, (ANR-23-CE11-0034-01), project: DNA Origami-based machines for epigenetic manipulation of gene transcription (acronym: ChromOrigami), 01/01/2024-31/12/2026, French coordinator: L. Tora, collaboration with the teams of N. Molina (IGBMC), M. Poirier, Ohio State University (Department of physics, OSU, USA), US coordinator, and C. Castro (OSU, USA).
  • ANR Programme 2022 (ANR-22-CE11-0013-01_ACT), project: Structure and function of human ATAC HAT complex (acronym ATAC); 01/10/2022-30/09/2025, Coordinator: G. Papai (IGBMC), collaboration with L. Tora team.
  • NIH MIRA grant (USA), R35GM139564, Mechanisms of chromatin regulation of transcription. Coordinator: M. Poirier, Ohio State University (Department of physics, OSU, USA), co-PI. Tora group (IGBMC); 01/02/2022-31/08/2026.
  • FRM (Fondation pour la Recherche Médicale) (EQU-2021-03012631), "Équipe labélisé FRM", project: Characterization of a new transcription initiation machinery functioning during mammalian oogenesis; 01/12/2021-30/11/2024,
  • ANR Programme 2020 (ANR-20-CE12-0014-02), project: Coactivator, Partner: D. Devys (Tora team). Coordinator: D. Helmlinger (CRBM, Montpellier) 01/04/2021-28/02/2025.
  • ANR Programme 2020 (ANR-20-CE12-0017-03), project: Functions and dysfunctions of the transcription/repair factor TFIIH (acronym TFIIH) Coordinator: F. Coin (IGBMC), collaboration with L. Tora team; 01/01/2021-30/06/2024.
  • ANR PRCI Programme 2019, (EpiCAST-19-CE12-0029-01), project: Epigenetic complex assembly in space and time (acronym: EpiCAST), French coordinator: L. Tora, collaboration with HTM Timmers' (DKFZ, Freiburg, Germany) team; 01/01/2020-31/30/06/2023.
  • NSF (National Science foundation, USA), Emerging Frontiers in Research and Innovation 2019 (EFRI), SUBAWARD N° 60072367;, project: DNA origami tools to engineer chromatin structure and function in live cells; with four US groups. Coordinator: C. Castro (OSU, USA); 01/09/2019-31/08/2023
  • ANR Programme 2019 (PICen-19-CE11-0003-02), project: Structure and function of endogenous yeast TFIID-containing complexes (acronym PICen); Coordinator: G. Papai (IGBMC), collaboration with L. Tora team; 01/10/2019-30/09/2022.
  • ANR Programme 2018 (ANR-18-CE12-0026), SAGA-Retina, Coordinator: D. Devys (Tora team). 01/01/2019-31/12/2021;
  • NIH RO1 grant (USA), 5R01GM131626-02, coordinator: M. Poirier, Ohio State University (OSU, USA): Understanding how two related mammalian histone acetyl transferase co-activator complexes, SAGA and ATAC, differentially regulate chromatin dynamics and transcription. 01/02/2019-31/01/2023.
  • ANR Programme 2015, (ANR-15-CE11-0022-02), SAGA2, Structure, activité et analyse génomique de co-activateur SAGA, Two groups. Applicant D. Devys. Partner; 01/10/2015-30/09/2018.
  • ERC Advanced Grant-2013, project: From birth to action: regulation of gene expression through transcription complex biogenesis, (acronym BIRTOACTION) 01/01/2014-31/12/2018.

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News

When protein complex construction and protein synthesis occur simultaneously

The activity of our cells is regulated by multiprotein complexes, essential for their functioning. In a study published in Nature Structural &…

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Awards and recognitions

Laszlo Tora -

  • Elected as a member of Academia Europaea, in 2016

  •                                                                                     Academia Europaea - Wikipedia

  • Elected as a member of Faculty Opinions (originally called F1000Prime) in 2014. Member of the Cell Biology/Control of Gene Expression Faculty.

  •                                                                                          F1000Prime is now Faculty Opinions - Faculty Opinions Blog

  • ERC Advanced Grant - European Research Council, in 2013.

  •                                                                                

  • Doctoral and research supervision award for high level of scientific activity with teaching from CNRS, in 2013.
  • Etancelin Grand Prize - Institut de France de l'Académie des Sciences - in 2011

  • L'Institut de France et la Grande Guerre  

  • Elected as a member of the Hungarian Academy of Sciences, Section of Biological Sciences, in 2010

  •                                                                                     History of the Hungarian Academy of Sciences | MTA

  • Scientific Prize - Helmholtz Humboldt Research award, in 2005

  •                                             

  • Elected as a member of the European Molecular Biology Organization (EMBO) in 2001

  •                                                                               Organisations

  • Silver Medal - CNRS - 2001

  •                                                            

  • One-year research scholarship within the framework of Hungarian-French scientific and technical cooperation and exchange programs (in 1985).

Publications

Development and stem cells - Cancer research - Rare diseases - Functional genomics and cancer