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EpiMic / Bierne

Applicants for a Marie Skłodowska-Curie Individual Fellowship are welcome


Epigenetics and Cellular Microbiology

Team Leader: Hélène Bierne



The EPIMIC team focuses on the long-term impact of pathogenic bacteria on health. We study the molecular basis of persistent bacterial infections, as well as the epigenetic consequences of these infections on host cells. This research aims to find new ways of treatment against recurrent infections, and against bacterial imprints that may contribute to the genesis of chronic and complex diseases, such as cancer and autoimmune and metabolic diseases.

Our model is the facultative intracellular bacterium Listeria monocytogenes, which, like viruses, has developed highly sophisticated mechanisms to deregulate and exploit signaling pathways in mammalian cells. It is noteworthy that several of these signaling pathways are also involved in carcinogenesis and other adverse health effects. Thus, through the study of Listeria, we can highlight the function of human proteins, whose deregulation could lead to both infectious and other diseases.

The BAHD1 chromatin-silencing complex.

We found that Listeria targets the human protein BAHD1 (Bierne et al., 2009) and show that this chromatin-bound factor defines a novel histone deacetylase repressive complex  involved in epigenetic regulation. BAHD1 acts by tethering chromatin regulators (MIER, HP1, MBD1, KAP1) and chromatin-modifying enzymes (HMT and HDAC) to sequence-specific transcription factors, enabling local chromatin compaction (Bierne et al., 2009)(Lebreton et al., 2011). BAHD1 controls placental development and cholesterol homeostasis (Lakisic et al., 2016) and plays a role in bacterial infections (Lebreton et al. 2011, Lebreton et al, 2014). In addition, we provide evidence that BAHD1-mediated heterochromatin formation could be linked to DNA methylation and may contribute to the spatial architecture of the genome (Libertini et al., 2015). 


The BAHD1 complex

Epigenetics, infection and immunity

Upon signaling induced by L. monocytogenes infection, the BAHD1 complex represses a set of immunity genes induced by interferons in epithelial cells. When bacteria secrete the protein LntA, this factor prevents the action of BAHD1 in the nucleus and selectively activates interferon-stimulated genes (Lebreton et al., 2011). LntA interacts directly with a central proline-rich domain of BAHD1 via a surface patch of conserved positive charges. Two lysines within this patch are required for LntA function (Lebreton et al., 2014).            



These results show that a bacterium can fine-tune the expression of immunity genes by controling negatively or positively the function of an epigenetic regulator.

LntA is a paradigm for the emerging class of bacterial effectors entering the nucleus and hijacking nuclear processes, termed “nucleomodulins” (Bierne and Cossart, 2012). Studying nucleomodulins can generate new insights into long-term impacts of infectious diseases. Our work now aims to characterize epimutations induced by these factors and by other bacterial stimuli, and to investigate whether these “pathoepimutations” reprogram host cells.

A role for type III interferons in bacterial infections

Interferons (IFNs) are secreted proteins of the cytokine family that regulate innate and adaptiveimmune responses to infection and tumor formation. Although the importance of IFNs in the antiviral response has long been appreciated, their role in bacterial infections is more complex. Bacterial infections are known to trigger the expression of type I and II IFNs. Our work recently highlighted that bacterial infections also activate the type III interferons (IFN-λ), which may be important modulators of the immune response to Gram-positive bacteria in epithelial tissues (Bierne et al., 2012)(Dussurget et al., 2014)(Odendall et al., 2014)..

The RalGAPβ mitotic regulator

Bacterial pathogens can also interfere with the eukaryotic cell cycle. Searching for host proteins that could be targeted by Listeria was an opportunity to discover a novel mitotic regulator. 

Illustration Hélène

 RalGAPβ is the non-catalytic β subunit of RalGAPa1/2β complexes, which negatively control the small GTPases RalA and RalB. We recently found that RalGAPβ localizes to mitotic cells and plays a role in the spindle assembly checkpoint and in cytokinesis (Personnic et al., 2014).

Publications (link to pubmed)


This research was supported by INRA, the French National Research Agency (ANR), the French Ligue de Recherche Contre le Cancer and the iXcore Research Fundation.