Minor Loops in Major Folds: Enhancer–Promoter Looping, Chromatin Restructuring, and Their Association with Transcriptional Regulation and Disease
Year: 2015
Type: review
Abstract: The organization and folding of chromatin within the nucleus can determine the outcome of gene expression.Recent technological advancements have enabled us to study chromatin interactions in a genome-wide manner at high resolution.These studies have increased our understanding of the hierarchy and dynamics of chromatin domains that facilitate cognate enhancer-promoter looping, defining the transcriptional program of different cell types.In this review, we focus on vertebrate chromatin long-range interactions as they relate to transcriptional regulation.In addition, we describe how the alteration of boundaries that mark discrete regions in the genome with high interaction frequencies within them, called topological associated domains (TADs), could lead to various phenotypes, including human diseases, which we term as "TADopathies." DNA Folding and Transcriptional Gene RegulationDNA is bound by a variety of histone proteins, noncoding RNAs, and transcription factors, collectively called chromatin.Packaging of chromatin within a eukaryotic nucleus can bring distant loci together, which may affect their transcriptional state.Numerous experiments have shown that the juxtaposition of two distant loci is not random, and their functional outcome depends upon the nature of interacting loci and the histone modifications they harbor.This information is encoded in the sequence of the loci that determines the transcription factors that bind to the DNA.Histone-modifying enzymes and complexes play a crucial role in regulating chromatin accessibility (for an in-depth review of how chromatin modifications regulate gene expression, refer to citations [1-3]).Understanding the determinants that organize this cell type-specific spatial arrangement of long DNA molecules is crucial in order to comprehend how genomes are regulated.Much of our understanding of eukaryotic gene expression has been gained by characterizing gene regulatory elements.Apart from the promoters that are quintessential for gene expression, distal regulatory elements control gene expression in a spatiotemporal manner.These elements include the following: "repressors," which can inhibit gene promoters; "insulators," which
Source: PLoS Genetics
Authors: Navneet Matharu, Nadav Ahituv
Institution: University of California, San Francisco
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,043
Awards: Massively parallel, in vivo functional testing of regulatory elements, G187421119, Characterization of neuronal gene regulatory elements associated with epilepsy, Pharmacogenomics of Membrane Transporters, Identification & functional characterization of SIM1 obesity-associated variants, Integrative interpretation of the organismal consequences of non-coding variation, UCSF Nutrition Obesity Research Center, Pharmacogenetics of Membrane Transporters
OpenAlex ID: W2217100747