Chromatin’s stained glass
Reini Luco and her research team are looking for novel mechanisms of alternative splicing regulation amongst chromatin regulators. By using a well established and inducible human model system of cell reprogramming, the epithelial-to-mesenchymal transition, they aim at understanding which is the dynamic interplay between histone modifications and alternative splicing to demonstrate for the first time the real physiological impact of chromatin on cell-specific splicing.
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.
Using different approaches, from genome-wide to gene-specific, we have shown that histone marks are sufficient and necessary to induce the changes in alternative splicing necessary for an EMT. Moreover, these splicing-associated histone marks play a combinatorial role coordinating the alternative splicing of functionally-related genes in a highly dynamic way, suggesting that rapid splicing responses could also be regulated by epigenetics.
Our group aims at the better understanding of the role of epigenetics 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 are using genome-wide deep sequencing approaches (RNA-seq, ChIP-seq, CUT&Run, 4C-seq), that combined with state-of-the-art molecular and cell biology tools, such as CRISPRS-dCas9 tools, will help us better understand the impact of histone modifications and 3D chromatin organization in establishing a new splicing program necessary for the cell reprogramming during EMT.
• 2013: Appointed Group Leader (CNRS-CR1, permanent position), IGH, Montpellier, France
• 2007-2012: Postdoctoral fellow, National Institutes of Health, National Cancer Institute, Bethesda, USA. Tom Misteli’s Lab
• 2007 PhD, Hospital Clinic de Barcelona, Barcelona, Spain. Jorge Ferrer’s Lab
• CNRS Bronze Medal, 2016
• Member of Montpellier’s Laboratories of Excellence: LABEX EpiGenMed, 2014
• Marie Curie Career Integration Grant, 2013
• Member of the EpiGeneSys ”Research Integrating System Biology and Epigenetics”, 2013
• Laureate of the ATIP-AVENIR programme of excellence, 2013
• The Center for Cancer Research top Science advances award, National Institutes of Health, 2011
• NCI Intramural Career Development Innovation Award, National Institutes of Health, 2010
Nov 2016, Nat Struct Mol Biol
May 2015, Nat Struct Mol Biol
Aug 2011, Curr Opin Genet Dev