
Molecular Basis of Chromatin and Transcription Regulation
Molecular Basis of Chromatin and Transcription Regulation
Our team "Molecular Basis of Chromatin and Transcription Regulation" studies eukaryotic epigenetic mechanisms that are essential for cell homeostasis and for the development of organisms. We are particularly characterizing the molecular basis of epigenetic mechanisms to decipher their involvement in the regulation of nuclear processes and to understand their physiological roles. We then use this knowledge to determine how mutations in epigenetic effectors can lead to many different pathologies. We are also implementing strategies to characterize small molecules that inhibit or regulate the activity of epigenetic effectors in order to help the development of drug candidates targeting cancers and neglected diseases (malaria, leishmaniasis, schistosomiasis, Chagas disease).
Our objectives are to combine these three axes of research to help decipher the cause of epigenetic diseases and to help the development of epigenetic therapies. Our studies notably rely on biochemical, biophysical and structural biology analyses. However, we are developing all of our projects within the framework of integrative biology strategies that combine in vitro, in cellulo and in vivo analyzes. If the latter two aspects are mainly pursued through collaborative work, our goal is to integrate more and more these different integrative biology investigations directly within our team. In particular, we now use the zebrafish animal model within the team to address our three axes of research (mechanisms, pathologies and small molecules), and thus characterize the structure/function relationships of our epigenetic targets.
Our scientific projects study three types of epigenetic effectors in particular: deacetylases, histone chaperones and, more recently, cohesin. Although these three types of effectors have distinct activities, our primary epigenetic targets are all functionally related, our ultimate goal being to characterize their physical and functional interrelationships. In addition to our epigenetic biological research axes, our team has been developing for many years the technology of protein complexes reconstitution by multi-expression in bacterial hosts. This technology, and our associated know-how, supports all of our scientific projects, but is also recognized by many laboratories that have either acquired it or are collaborating with our team to use it. Thus, our team also develops specific collaborative projects, which in return opens up new perspectives for our own scientific projects.
Members
Researchers
PhD students
Engineers
Technicians
Funding and partners
A 2-year post-doctoral position is available in our team on the ADAT projects (see our 2021 publication in Nucleic Acids Research).
For more information, please contact Christophe Romier (romier(at)igbmc.fr).
Publications
2021
Species-selective targeting of pathogens revealed by the atypical structure and active site of Trypanosoma cruzi histone deacetylase DAC2
- Martin Marek
- Elizabeth Ramos-Morales
- Gisele F A Picchi-Constante
- Theresa Bayer
- Carina Norström
- Daniel Herp
- Policarpo A Sales-Junior
- Eloise P Guerra-Slompo
- Kristin Hausmann
- Alokta Chakrabarti
- Tajith B Shaik
- Annika Merz
- Edouard Troesch
- Karin Schmidtkunz
- Samuel Goldenberg
- Raymond J Pierce
- Marina M Mourão
- Manfred Jung
- Johan Schultz
- Wolfgang Sippl
- ...
Cell Reports ; Volume: 37
The structure of the mouse ADAT2/ADAT3 complex reveals the molecular basis for mammalian tRNA wobble adenosine-to-inosine deamination
- Elizabeth Ramos Morales
- Efil Bayam
- Jordi del Pozo Rodriguez
- Thalia Salinas-Giegé
- Martin Marek
- Peggy Tilly
- Philippe Wolff
- Edouard Troesch
- Eric Ennifar
- Laurence Drouard
- Juliette Godin
- Christophe Romier
Nucleic Acids Research ; Volume: 49 ; Page: 6529-6548
Binding Free Energy (BFE) Calculations and Quantitative Structure-Activity Relationship (QSAR) Analysis of Schistosoma mansoni Histone Deacetylase 8 (smHDAC8) Inhibitors
- Conrad V. Simoben
- Ehab Ghazy
- Patrick Zeyen
- Salma Darwish
- Matthias Schmidt
- Christophe Romier
- Dina Robaa
- Wolfgang Sippl
Molecules ; Volume: 26
Citrullination of pyruvate kinase M2 by PADI1 and PADI3 regulates glycolysis and cancer cell proliferation
- Sébastien Coassolo
- Guillaume Davidson
- Luc Negroni
- Giovanni Gambi
- Sylvain Daujat
- Christophe Romier
- Irwin Davidson
Nature Communications ; Volume: 12
2020
Design, synthesis, and biological evaluation of dual targeting inhibitors of histone deacetylase 6/8 and bromodomain BRPF1
- Ehab Ghazy
- Patrik Zeyen
- Daniel Herp
- Martin Hügle
- Karin Schmidtkunz
- Frank Erdmann
- Dina Robaa
- Matthias Schmidt
- Elizabeth Morales
- Christophe Romier
- Stefan Günther
- Manfred Jung
- Wolfgang Sippl
European Journal of Medicinal Chemistry ; Volume: 200 ; Page: 112338
2019
Structure‐Based Design, Synthesis, and Biological Evaluation of Triazole‐Based smHDAC8 Inhibitors
- Dmitrii V. Kalinin
- Sunit K. Jana
- Maxim Pfafenrot
- Alokta Chakrabarti
- Jelena Melesina
- Tajith B. Shaik
- Julien Lancelot
- Raymond J. Pierce
- Wolfgang Sippl
- Christophe Romier
- Manfred Jung
- Ralph Holl
ChemMedChem ; Volume: 15 ; Page: 571-584
One-Atom Substitution Enables Direct and Continuous Monitoring of Histone Deacylase Activity
- Matthes Zessin
- Zsófia Kutil
- Marat Meleshin
- Zora Nováková
- Ehab Ghazy
- Diana Kalbas
- Martin Marek
- Christophe Romier
- Wolfgang Sippl
- Cyril Bařinka
- Mike Schutkowski
Biochemistry ; Volume: 58 ; Page: 4777-4789
Structure–Reactivity Relationships on Substrates and Inhibitors of the Lysine Deacylase Sirtuin 2 from Schistosoma mansoni ( Sm Sirt2)
- Daria Monaldi
- Dante Rotili
- Julien Lancelot
- Martin Marek
- Nathalie Wössner
- Alessia Lucidi
- Daniela Tomaselli
- Elizabeth Ramos-Morales
- Christophe Romier
- Raymond J. Pierce
- Antonello Mai
- Manfred Jung
Journal of Medicinal Chemistry ; Volume: 62 ; Page: 8733-8759
Synthesis and Biological Investigation of Phenothiazine-Based Benzhydroxamic Acids as Selective Histone Deacetylase 6 Inhibitors
- Katharina Vögerl
- Nghia Ong
- Johanna Senger
- Daniel Herp
- Karin Schmidtkunz
- Martin Marek
- Martin Müller
- Karin Bartel
- Tajith Shaik
- Nicholas Porter
- Dina Robaa
- David W. Christianson
- Christophe Romier
- Wolfgang Sippl
- Manfred Jung
- Franz Bracher
Journal of Medicinal Chemistry ; Volume: 62 ; Page: 1138-1166
2018
Characterization of Histone Deacetylase 8 (HDAC8) Selective Inhibition Reveals Specific Active Site Structural and Functional Determinants
- Martin Marek
- Tajith Shaik
- Tino Heimburg
- Alokta Chakrabarti
- Julien Lancelot
- Elizabeth Ramos-Morales
- Cyrielle da Veiga
- Dmitrii Kalinin
- Jelena Melesina
- Dina Robaa
- Karin Schmidtkunz
- Takayoshi Suzuki
- Ralph Holl
- Eric Ennifar
- Raymond Pierce
- Manfred Jung
- Wolfang Sippl
- Christophe Romier
Journal of Medicinal Chemistry ; Volume: 61 ; Page: 10000-10016
News

Four IGBMC members are winners of the IdEx Research 2021 call for projects
Four members of the IGBMC are winners of the IdEX Research 2021 call for projects, announced the University of Strasbourg on 16 June 2021. This award…
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