Abstract

It is widely known that epigenetic modifications are important in regulating transcription, but several have also been reported in alternative splicing. The regulation of pre-mRNA splicing is important to explain proteomic diversity and the misregulation of splicing has been implicated in many diseases. Here, we give a brief overview of the role of epigenetics in alternative splicing and disease. We then discuss the bioinformatics methods that can be used to model interactions between epigenetic marks and regulators of splicing. These models can be used to identify alternative splicing and epigenetic changes across different phenotypes.This article is part of a discussion meeting issue ‘Frontiers in epigenetic chemical biology’.

Highlights

  • Epigenetic modifications change the regulation of the genome without changing the DNA sequence

  • Our increased knowledge of epigenetics significantly improves our understanding of gene regulation and biological pathways that are regulated epigenetically

  • We focus on bioinformatics methods that have been developed to understand splicing regulation

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Summary

Introduction

Epigenetic modifications change the regulation of the genome without changing the DNA sequence. Chemical modifications such as methylation, acetylation and phosphorylation are known to alter histone function Each of these modifications is reversible, and this has increased the prospects of epigenetic markers as therapeutic drug targets [1,2]. While DNA cytosine modifications are known to influence transcription, there is growing evidence for its role in the regulation of alternative splicing [8,9,10]. Trans-acting splicing factors can bind to the spliceosome or to bound or open cis-elements to direct binding of the spliceosome to the pre-mRNA and alternative splicing. We focus on bioinformatics methods that have been developed to understand splicing regulation This includes the regulatory relationships that govern splicing and differences in isoform expression relating to disease. Though not exhaustive, examples on each topic while directing the reader to comprehensive reviews

Epigenetics and alternative splicing
Alternative splicing and disease
RNA-seq analysis of differential alternative splicing
Bioinformatics modelling in epigenetics and splicing
Splicing regulation networks
Functional isoform networks
Current limitations and challenges
Conclusion
47. Zhang C et al 2010 Integrative modeling defines
67. Lefebvre C et al 2010 A human B-cell interactome
44. Margulies M et al 2006 Corrigendum: genome
Findings
78. Petryszak R et al 2014 Expression Atlas

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