title: Transcriptional enhancers: functional insights and role in human disease.
abstract: In recent years, studies of cis-regulatory mechanisms have evolved from a predominant focus on promoter regions to the realization that spatial and temporal gene regulation is frequently driven by long-range enhancer clusters that operate within chromosomal compartments. This increased understanding of genome function, together with the emergence of technologies that enable whole-genome sequencing of patients' DNAs, open the prospect of dissecting the role of cis-regulatory defects in human disease. In this review we discuss how recent epigenomic studies have provided insights into the function of transcriptional enhancers. We then present examples that illustrate how integrative genomics can help uncover enhancer sequence variants underlying Mendelian and common polygenic human disease.
authors.affiliation: Department of Medicine, Imperial College London, London W12 0NN, United Kingdom; Genomic Programming of Beta-cells Laboratory, Institut d'Investigacions August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 08036 Barcelona, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Miguel-Escalada
authors.affiliation: CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 08036 Barcelona, Spain; Division of Endocrinology, Germans Trias i Pujol University Hospital and Research Institute and Josep Carreras Leukaemia Research Institute, 08036 Barcelona, Spain; Josep Carreras Leukaemia Research Institute, 08036 Barcelona, Spain.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Pasquali
authors.affiliation: Department of Medicine, Imperial College London, London W12 0NN, United Kingdom; Genomic Programming of Beta-cells Laboratory, Institut d'Investigacions August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 08036 Barcelona, Spain. Electronic address: j.ferrer@imperial.ac.uk.
authors.forename: Jorge
authors.initials: J
authors.lastname: Ferrer
mesh_terms: D004742:Enhancer Elements, Genetic; D044127:Epigenesis, Genetic / Q000235:genetics; D005786:Gene Expression Regulation; D030342:Genetic Diseases, Inborn / Q000235:genetics* / Q000473:pathology; D006801:Humans; D014158:Transcription, Genetic