Current challenges in understanding the role of enhancers in disease.

Autor: Zaugg JB; European Molecular Biology Laboratory, Heidelberg, Germany., Sahlén P; Science for Life Laboratory, KTH - Royal Institute of Technology, Solna, Sweden., Andersson R; Section for Computational and RNA Biology, Department of Biology, University of Copenhagen, Copenhagen, Denmark.; The Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Alberich-Jorda M; Department of Hemato-oncology, Institute of Molecular Genetics of the CAS, Prague, Czech Republic.; Childhood Leukaemia Investigation Prague, Department of Pediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University in Prague, University Hospital Motol, Prague, Czech Republic., de Laat W; Hubrecht Institute-KNAW, Oncode Institute and University Medical Center Utrecht, Utrech, Netherlands., Deplancke B; Laboratory of Systems Biology and Genetics, Institute of Bio-engineering, School of Life Sciences, EPFL, Lausanne, Switzerland., Ferrer J; Centre for Genomic Regulation, the Barcelona Institute of Science and Technology, Barcelona, Spain.; Centro de Investigación Biomédica en red Diabetes y enfermedades metabólicas asociadas (CIBERDEM), Madrid, Spain.; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK., Mandrup S; The Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Functional Genomics and Metabolism Research Unit, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark., Natoli G; IEO, European Institute of Oncology - IRCCS, Milan, Italy., Plewczynski D; Laboratory of Functional and Structural Genomics, Centre of New Technologies, University of Warsaw, Warsaw, Poland., Rada-Iglesias A; Institute of Biomedicine and Biotechnology of Cantabria (IBBTEC), CSIC/University of Cantabria, Santander, Spain., Spicuglia S; TAGC, UMR 1090, Aix-Marseille University, INSERM, Marseille, France. salvatore.spicuglia@inserm.fr.; Equipe Labellisée, LIGUE Contre le Cancer, Marseille, France. salvatore.spicuglia@inserm.fr.
Jazyk: angličtina
Zdroj: Nature structural & molecular biology [Nat Struct Mol Biol] 2022 Dec; Vol. 29 (12), pp. 1148-1158. Date of Electronic Publication: 2022 Dec 08.
DOI: 10.1038/s41594-022-00896-3
Abstrakt: Enhancers play a central role in the spatiotemporal control of gene expression and tend to work in a cell-type-specific manner. In addition, they are suggested to be major contributors to phenotypic variation, evolution and disease. There is growing evidence that enhancer dysfunction due to genetic, structural or epigenetic mechanisms contributes to a broad range of human diseases referred to as enhanceropathies. Such mechanisms often underlie the susceptibility to common diseases, but can also play a direct causal role in cancer or Mendelian diseases. Despite the recent gain of insights into enhancer biology and function, we still have a limited ability to predict how enhancer dysfunction impacts gene expression. Here we discuss the major challenges that need to be overcome when studying the role of enhancers in disease etiology and highlight opportunities and directions for future studies, aiming to disentangle the molecular basis of enhanceropathies.
(© 2022. Springer Nature America, Inc.)
Databáze: MEDLINE
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