Interplay between chromatin and splicing

FISZBEIN, ANA; GODOY HERZ, MICAELA A; GÓMEZ ACUÑA, LUCIANA I; KORNBLIHTT, ALBERTO

Chromatin Regulation and Dynamics

Elsevier

Año: 2016;

Alternative splicing is a fundamental mRNA processing event that explains how a high biological complexity is achieved from a limited number of genes. By allowing each gene to encode several polypeptide variants, alternative splicing largely expands the coding capacities of the genetic information. Regulation of splicing and alternative splicing is important to determine normal cell functioning, cell differentiation and responses to external cues. Moreover, misregulation of splicing is frequently associated to hereditary disease and cancer. As most splicing or splicing commitment takes place co-transcriptionally, an additional layer of splicing regulation based on the regulation of transcription is opened. As transcription occurs through chromatin, any particular factor affecting chromatin structure will also alter transcription and therefore may eventually affect splicing decisions. A complex picture emerges in which splicing regulation not only depends on chromatin structure determined by specific histone marks, but also by DNA methylation and nucleosome positioning. Moreover, in actively transcribed genes, transcription and alternative splicing machineries and dynamics affect chromatin structure. This chapter discusses the multiple layers of co-transcriptional regulation of splicing and alternative splicing in which chromatin structure plays a fundamental role by providing a dynamic scaffold for interactions between the splicing and transcription machineries. We focus on evidence that explains how chromatin organization can impact on the regulation of splicing and alternative splicing acting in coordination with recruitment of splicing factors, adaptor proteins and co-transcriptional features.