An epigenetic view on alternative splicing

Genome-wide analysis indicate that alternative splicing of mRNA precursors (pre-mRNAs) affects the vast majority of human genes. Alternative splicing provides a fundamental mechanism to increases transcriptome complexity, allowing the production of two or more mRNA variants that often encode proteins with different, sometimes opposite functions. Its importance is underscored by the observation that misregulated alternative splicing can lead to human diseases. Pre-mRNA splicing has long been known to be regulated by cis-acting sequence elements and trans-acting protein factors. In higher eukaryotes, it mostly occurs co-transcriptionally so that it is not surprising that a role for chromatin and epigenetic factors in the regulation of exon inclusion is now emerging. In this review, we will discuss the most recent findings on the roles played by chromatin structure on the modulation of the cotranscriptional splicing reactions. In particular, we will focus our attention on how the modulation of the transcribing RNA polymerase II, the changes in nucleosome architecture and the presence of different histone modifications contribute to the regulation of the splicing process.