Intragenic chromatin modifications: a new layer in alternative splicing regulation

The multiple steps that contribute to gene expression in the metazoan nucleus are highly integrated and regulated. Most of pre-mRNA processing is believed to occur co-transcriptionally and choices regarding alternative processing reactions are influenced by transcription. Several articles published in the last year unveiled a connection between chromatin structure and the splicing process, strengthening a view in which the dynamic of intragenic chromatin modifications has an important role regulating alternative splicing (AS) choices. We have recently shown that both neuronal cell depolarization and the use of double stranded small RNAs targeting intragenic regions can modulate AS through chromatin remodeling, taking advantage of the kinetic coupling between splicing and transcription. Here, we discuss the many ways in which intragenic chromatin can participate in alternative splicing regulation.