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Laboratory | Stress response | Genomics


Nuclear Regulation and Stress

​​​​​​​Control of RNA polymerase III-transcribed genes expression in response to various stresses. Characterization of pathways involved in the modulation of transcriptional activity. Development of biochemical techniques to exhaustively identify proteins interfering with the transcription machinery. Studies on the influence of RNA polymerase III transcription on retrotransposon Ty1 integration.​

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Published on 19 June 2019

​Team Leaders
Joël ACKER

Christine CONESA

Olivier LEFEBVRE

+33 1 69 08 65 61
joel.acker@cea.fr
+33 1 69 08 37 96
christine.conesa@cea.fr
+33 1 69 08 46 20
olivier.lefebvre@cea.fr
​Staff
Joël ACKER
Christine CONESA
Olivier LEFEBVRE
Elise RABUT


Researcher
Researcher
Researcher
Research Engineer

 


Carine (Lab Alumni), Olivier, Verónica (Lab Alumni), Ewa (Lab Alumni), Joël, Christine, Indranil (Lab Alumni)

This team is part of I2BC (Nuclear Regulation and Stress).

The regulation of RNA polymerase III transcription (Pol III) plays a major role in the adaptation of cell growth in response to physiological changes or environmental modifications. Moreover, the level of RNA synthesized by Pol III is abnormally high in tumour cells. Therefore, our research focuses on the regulation of transcription levels of Pol III-transcribed genes in response to various stresses in yeast cells. Our aim is to decipher networks (conserved from yeast to humans) involved in the modulation of Pol III transcriptional activity from signal perception to components of the transcription machinery. On the other hand, many DNA-dependent processes occur at or close to Pol III-transcribed genes and interfere with the Pol III transcription machinery. For instance, the integration of retroviruses and LTR-retrotransposons is not random in vivo. Genome wide studies indicated a clear preference for Ty1 retrotransposon integration upstream of Pol III-transcribed genes in the yeast Saccharomyces cerevisiae. Therefore, we have recently started a new project in collaboration with the group of Dr Pascale Lesage (IUH, Paris Diderot) in order to characterize the role of Pol III transcription in the selective integration of Ty1.

Conservation of the role of transcription for integration of retroelements
A common targeting mechanism between retroelements (LTR-retrotransposon as Ty1 and retrovirus): the tethering of
integration complexes to the cell genome through an interaction between the integrase of the retroelement and cellular proteins (blue light colored) involved in gene transcription.
​Pascale Lesage (IUH, Paris Diderot)​

To obtain a global view of all the phenomenon that occur on Pol III-transcribed genes, we first thought to identify all the
players directly involved by developing innovative approaches in biochemistry. We have set up with success our own tandem chromatin affinity purification procedure (TChAP) after in vivo cross-link to identify the proteins associated with the Pol III machinery in normal growth conditions but also in response to stresses.


Schematic of TChAP procedure
Nguyen et al. Gene 2015

Another part of our projects is dedicated to the fine dissection of the molecular mechanisms that enable the cell to adjust its transcription level to environmental conditions. Thus, using genome wide, genetic and in vitro approaches we are currently investigating the putative role in Pol III transcription and regulation of the new factors we identified using our TchAP strategy.

Our research has been or is supported by the ARC and ANR.