Enhancer Logic and Mechanics in Development and Disease
Abstract
Enhancers are distally located genomic cis-regulatory elements that integrate spatiotemporal cues to coordinate gene expression in a tissue-specific manner during metazoan development. Enhancer function depends on a combination of bound transcription factors and cofactors that regulate local chromatin structure, as well as on the topological interactions that are necessary for their activity. Numerous genome-wide studies concur that the vast majority of disease-associated variations occur within non-coding genomic sequences, in other words the 'cis-regulome', and this underscores their relevance for human health. Advances in DNA sequencing and genome-editing technologies have dramatically expanded our ability to identify enhancers and investigate their properties in vivo, revealing an extraordinary level of interconnectivity underlying cis-regulatory networks. We discuss here these recently developed methodologies, as well as emerging trends and remaining questions in the field of enhancer biology, and how perturbation of enhancer activities/functions results in enhanceropathies.
Citations
Development of enhancer-trapping and -detection vectors mediated by the Tol2 transposon in zebrafish
Enhancer prediction in the human genome by probabilistic modelling of the chromatin feature patterns
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