title: Immune disease-associated variants in gene enhancers point to BET epigenetic mechanisms for therapeutic intervention.
abstract: Genome-wide association studies have identified thousands of single nucleotide polymorphisms in the human genome that are statistically associated with particular disease traits. In this Perspective, we review emerging data suggesting that most single nucleotide polymorphisms associated with immune-mediated diseases are found in regulatory regions of the DNA - parts of the genome that control expression of the protein encoding genes - rather than causing mutations in proteins. We discuss how the emerging understanding of particular gene regulatory regions, gene enhancers and the epigenetic mechanisms by which they are regulated is opening up new opportunities for the treatment of immune-mediated diseases, focusing particularly on the BET family of epigenetic reader proteins as potential therapeutic targets.
authors.affiliation: Epigenetics DPU, Immuno-Inflammation Therapy Area Unit, GlaxoSmithKline, Medicines Research Centre, Stevenage SG1 2NY, UK.
authors.forename: David F
authors.initials: DF
authors.lastname: Tough
authors.affiliation: Epigenetics DPU, Immuno-Inflammation Therapy Area Unit, GlaxoSmithKline, Medicines Research Centre, Stevenage SG1 2NY, UK.
authors.forename: Rab K
authors.initials: RK
authors.lastname: Prinjha
mesh_terms: D004742:Enhancer Elements, Genetic; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007154:Immune System Diseases / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide
chemical_list: D009687:Nuclear Proteins
keywords: GWAS; autoimmunity; bromodomain; enhancer; epigenetic gene regulation; histone; inflammation; super enhancer