Gil AstGil Ast
Chair, Department of Human Molecular Genetics & Biochemsitry
Sackler Medical School
Tel Aviv University, Israel


Presentation Title: How Chromatin organization and epigenetics talk with alternative splicing

Presentation Time: Sunday, July 21 9:00 AM - 10:00AM

 Room: Hall 1




The importance of RNA and chromatin in the multiple levels of regulation that ensure proper functioning of the eukaryotic transcriptome and proteome has been increasingly recognized in recent years. Converging lines of evidence have led to a clearer realization that many of these processes are interrelated. For example, there is continuous feed-forward crosstalk among the processes of chromatin organization, transcription, and pre-mRNA splicing. Furthermore, it has now become apparent that chromatin structure and epigenetic markers influence the recognition of exons and splice site choices. The multiple layers of regulation that function jointly in chromatin organization, transcription, and RNA processing will be presented.


The Ast's Group

Alternative splicing is a mechanism by which more than one mRNA transcripts are generated from the same mRNA precursor. Recent findings suggest that almost all the human genes undergo alternatively spliced, and we demonstrated that humans contain the highest level of alternative splicing. Alternative splicing can be specific to tissue type, environment or developmental stage. Splice variants have also been implicated in various diseases including cancer. Detection of these variants will enhance our understanding of the complexity of the human genome and provide disease-specific and prognostic biomarkers. Our group has made seminal contributions to our understanding of the complexity in genomic expression through alternative mRNA splicing and the involvement of this process in genetic disorders and cancer.

The broad focus of our research is on pre-mRNA splicing regulation and the importance of alternative splicing in generating transcriptomic diversity unique to our species. We also study the potential link between DNA packaging and splicing, and are interested in the effects nucleosomal positioning, specific histone modifications and other epigenetic characteristics have on pre-mRNA processing. An increasing body of evidence indicates that transcription and splicing are coupled and it is accepted that chromatin organization and DNA modification regulate transcription. Little is known, however, about the cross-talk between chromatin structure and splicing. We also study splicing-related genetic diseases like the neurodegenerative disease Familial Dysautonomia and the link between splicing and various cancer types. Finally, we study the role splicing plays in microRNA (miRNA) regulation as well.