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Κυριακή 3 Ιουνίου 2018

Enhancer Logic and Mechanics in Development and Disease

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Publication date: Available online 11 May 2018
Source:Trends in Cell Biology
Author(s): Ryan Rickels, Ali Shilatifard
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.



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