Genomic Views of Distant-Acting Enhancers

By Axel Visel, Edward M. Rubin, Len A. Pennacchio. Nature, 2009

635 citations recorded by the source corpus.

In contrast to protein-coding sequences, the significance of variation in non-coding DNA in human disease has been minimally explored. A great number of recent genome-wide association studies suggest that non-coding variation is a significant risk factor for common disorders, but the mechanisms by which this variation contributes to disease remain largely obscure. Distant-acting transcriptional enhancers — a major category of functional non-coding DNA — are involved in many developmental and disease-relevant processes. Genome-wide approaches to their discovery and functional characterization are now available and provide a growing knowledge base for the systematic exploration of their role in human biology and disease susceptibility.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/dc86c8ceff4bf1049bd47c3fbe210c8614df9163

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Citations in the corpus

PEDLA: predicting enhancers with a deep learning-based algorithmic framework (2016, background): “The first genome-scale efforts to identify enhancers were based on evolutionary sequence conservation (19-22) because regulatory sequences are likely to evolve under negative evolutionary selection (23-25).”
A unique chromatin signature uncovers early developmental enhancers in humans (2010, methodology): “Specificity of our reporter assays was validated by assaying an extensive set of negative controls (Supplementary Table 4): (1) five class I elements; (2) four nonconserved genomic regions in proximity of four of the tested class II elements; (3) four human adult-tissue-specific enhancers that shoul”
Transcriptional enhancers: from properties to genome-wide predictions (2014, background): “Understanding enhancers is currently an area of great interest, as there is an increasing appreciation of their importance not only in developmental gene expression but also in evolution and disease 5–7 .”
Extensive Promoter-centered Chromatin Interactions Provide a Topological Basis for Transcription Regulation (2012, neutral): “Moreover, many remote enhancers could be embedded in intronic regions of other distantly located genes (Visel et al., 2009), making it notoriously difficult to relate enhancers to their specific target genes.”
A Mammalian enhancer trap resource for discovering and manipulating neuronal cell types (2016, methodology): “Distal enhancers are known to regulate tissue specific expression of genes, especially in the forebrain (Nord et al., 2013; 2015; Visel et al., 2009; 2013) and to regulate activity-dependent gene expression (Kim et al., 2010).”
Histone H3K27ac separates active from poised enhancers and predicts developmental state (2010, background): “Global identification of these regions as well as their contribution to target gene expression has been challenging because enhancers can often reside thousands of base pairs away from their target of regulation (1, 2).”
Annotating non-coding regions of the genome (2010, background): “SNPs in many non-coding regions have been linked to disease in genome-wide association (GWA) studie”
Charting histone modifications and the functional organization of mammalian genomes (2011, background): “Enhancers are DNA elements that recruit transcription factors, RNAPII and chromatin regulators to positively influence transcription at distal promoter”
Gene regulation by the act of long non-coding RNA transcription (2013, background): “lncRNA transcription creating a permissive chromatin environment Enhancers are genetic elements that bind transcription factors facilitating transcription machinery assembly at nearby promoters [90,91].”
Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder (2018, neutral): “The majority of disease-associated genetic variation lies in noncoding regions (5) enriched for noncoding RNAs (ncRNAs) and cis-regulatory elements that regulate gene expression and splicing of their cognate coding gene targets (6, 7).”