Heterochromatin and Polycomb-marked gene Silencing by RNA decay

We have recently discovered that the highly conserved LSM2-8 complex mediates a mechanism of RNA degradation that selectively targets H3K27me3-marked genes in C. elegans, revealing that in animals heterochromatin, the compact compartment of the genome can be silenced by specific degradation of heterochromatic transcripts, and not only by transcriptional repression. Therefore, we are interested to focus our research on post-transcriptional mechanism(s) involved in heterochromatin silencing in general in higher eukaryotes. We expect that this research will deepen our understanding of regulation of gene expression in normal animal development and in response to the environment by integrating this novel RNA silencing regulation. In a longer perspective, our goal is to better understand the crosstalk between RNA and chromatin implicated in gene regulation, the initial targeting of the Polycomb H3K27me3 mark to the genome in C. elegans and mammals and ultimately to inflect abnormal gene expression in pathological contexts.

Therefore, we will investigate this novel mechanism of heterochromatic RNA degradation via the LSM2-8 complex and aim to understand the detailed mechanism of the LSM2-8 mediated silencing mechanism, the contribution of the transcriptional versus post-transcriptional repression; the feedback mechanism on the epigenetic state; and the conservation of this mechanism and level of regulation in mammals.

Currently, we focus particularly on:
1. Characterizing LSM-8 and the LSM2-8 mediated silencing mechanism
2. Studying the implication of this pathway in C. elegans development, fertility and innate immunity
3. Determining the conservation and the role of the LSM2-8 complex in murine Embryonic stem (ES) cells and CD4+ T cells differentiation

If you are interested to discuss Science or to join the team, please do not hesitate to contact me!