March 25th 2019 - 11AM

Dr. Geneviève Fourel, Laboratoire de Biologie et Modélisation Cellulaire (LBMC), ENS-Lyon

Location: Salle B501

Summary: My main interest is in dynamic genome organization and how grasping this dimension can help up in thinking about how a cell responds to cues from the environment, or differentiate, or turn to a cancer cell (see Refs.).

Picking in my own experimental work but also in the fantastic wealth of data available in the literature, I will illustrate the following points :

• Repeat sequences have a driving role in genome organization. Genome reorganization is often accompanied by repeat sequence transcription which presumably aid in genome remodeling, in particular during neuron stimulation. Of note, repeat sequences are conspicuously transcribed in cancer.

• The innate immunity / interferon pathway (Inn.Imm.Ifn-PathW) not only detects pathogens but also repeat sequences RNAs, as was first demonstrated in cancer . The highly conserved Inn.Imm.Ifn-PathW actually now appears as the first line, major cancer surveillance pathway of all organisms, and plays a key role in natural immune reaction and immune based-therapies by making the tumor immunogenic. I will explain why this phenomenon can be amplified with the use of Epidrugs that weaken heterochromatin, as now being implemented in the clinics.

• However, Inn.Imm.Ifn-PathW has also been found activated in a number of other physiological situations, and, when inquired, this correlated with significant transcription of repeat sequences. I will show that Inn.Imm.Ifn-PathW is activated at distinctive steps of some differentiation paths, in particular during neuron differentiation, where it can be interpreted to play a role in genome refolding after major genome reorganization. 

• Inn.Imm.Ifn-PathW is both allied and foe and anomalous activation thereof has further been implicated in a large array of pathologies. Data from the literature will be presented for Parkinson Disease (PD) and Amyotrophic lateral sclerosis (ALS) pointing to a major alteration of the heterochromatin compartment as the cause of Inn.Imm.Ifn-PathW activation, via the induction of repeat sequences transcription. I will speculate why the typifying process of "neuron stimulation" may make this cell type especially sensitive to alterations of heterochromatin, as well as to interpersonal variation in heterochromatin function.

Fourel, G., Lebrun, E. & Gilson, E. Protosilencers as building blocks for heterochromatin. Bioessays 24, 828-35 (2002).

Fourel, G., Magdinier, F. & Gilson, E. Insulator dynamics and the setting of chromatin domains. Bioessays 26, 523-32 (2004).

Fourel G., Genetic and epigenetic alterations of gene expression in the course of hepatocarcinogenesis. in: Liver gene expression, Editeurs : Tronche F, Yaniv M, 297-343, R.G. Landes Company, USA.(1994)

For more information, see the lab website.