Transcriptional enhancers: from prediction to functional assessment on a genome-wide scale
| Autor: | Mario A Filice, Tiegh Taylor, Sakthi D Moorthy, Nawrah Khader, Jennifer A. Mitchell, Luis E. Abatti, Ian C Tobias, Shanelle Mullany |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Epigenomics Gene Expression Computational biology Biology 03 medical and health sciences Gene Knockout Techniques 0302 clinical medicine Genome editing Genetics CRISPR Animals Humans Clustered Regularly Interspaced Short Palindromic Repeats Disease Epigenetics Enhancer Promoter Regions Genetic Molecular Biology Gene Transcription factor Binding Sites Genome Promoter General Medicine Chromatin 030104 developmental biology Enhancer Elements Genetic 030217 neurology & neurosurgery Biotechnology Transcription Factors |
| Zdroj: | Genome. 64(4) |
| ISSN: | 1480-3321 |
| Popis: | Enhancers are cis-regulatory sequences located distally to target genes. These sequences consolidate developmental and environmental cues to coordinate gene expression in a tissue-specific manner. Enhancer function and tissue specificity depend on the expressed set of transcription factors, which recognize binding sites and recruit cofactors that regulate local chromatin organization and gene transcription. Unlike other genomic elements, enhancers are challenging to identify because they function independently of orientation, are often distant from their promoters, have poorly defined boundaries, and display no reading frame. In addition, there are no defined genetic or epigenetic features that are unambiguously associated with enhancer activity. Over recent years there have been developments in both empirical assays and computational methods for enhancer prediction. We review genome-wide tools, CRISPR advancements, and high-throughput screening approaches that have improved our ability to both observe and manipulate enhancers in vitro at the level of primary genetic sequences, chromatin states, and spatial interactions. We also highlight contemporary animal models and their importance to enhancer validation. Together, these experimental systems and techniques complement one another and broaden our understanding of enhancer function in development, evolution, and disease. |
| Databáze: | OpenAIRE |
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