Reini F. Luco

Introduction

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.

Achievements

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.

Projects

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.