Chromatin and Splicing
Reini FERNANDEZ DE LUCO
IGH - UMR 9004
141, rue de la Cardonille
Phone: +33 4 34 35 99 12
Email: reini.luco@igh.cnrs.fr
Alternative splicing is one of the most general and important biological processes in the eukaryotic cell. It affects more than 90% of human genes, it is essential for protein diversity and any misregulation of the highly tissue-specific alternative splicing programs can lead to disease, such as cancer. However the mechanisms of cell-specific alternative splicing regulation are still largely unknown. Unexpectedly, in the past 15 years, chromatin and epigenetic modifications have been shown to play an important role in the regulation of alternative splicing. In particular, we have shown that non-coding RNAs and histone marks can talk to the splicing machinery via recruitment of chromatin/splicing-adaptor complexes.
Our group aims at the better understanding of the role of epigenetics and long non-coding RNAs in the onset and maintenance of tissue-specific splicing programs, using as an inducible cell reprogramming model system the epithelial-to-mesenchymal transition (EMT). For that purpose we will use state-of-the-art genome-wide deep sequencing approaches, combined with classical molecular and cell biology tools, to depict the molecular mechanisms of regulation of tissue-specific alternative splicing in a cancer-relevant model system.
In 2016, Reini Fernandez de Luco was awarded the CNRS Bronze Medal.
Keywords: alternative splicing, epigenetics, lncRNAs, genomics, EMT
Main publications :
- Gonzalez I, Munita R, Agirre E, Dittmer TA, Gysling K, Misteli T and Luco RF* A long non-coding RNA regulates alternative splicing via establishment of a splicing-specific chromatin signature. Nature Structural Molecular Biology 2015, 22(5):370-6.
- Luco RF The Non-Coding Genome: a universe in expansion for fine-tuning the coding world Genome Biology 2013, 14(11):314.
- Luco RF and Misteli T. More than a splicing code: Integrating the role of RNA, chromatin and non-coding RNA in alternative splicing regulation. Current Opinion in Genetics and Development 2011, 21:1-7.
- Luco RF, Allo M, Schor IE, Kornblihtt AR, Misteli T. Epigenetics in alternative pre-mRNA splicing. Cell 2011, 144 (1): 16-26.
- Luco RF, Pan Q, Tominaga K, Blencowe BJ, Pereira-Smith O, Misteli T. Regulation of alternative splicing by histone modifications. Science 2010, 327(5968):996-1000.
