title: The intriguing complexities of mammalian gene regulation: how to link enhancers to regulated genes. Are we there yet?
abstract: The information encoded in genomes supports the differentiation and function of the more than 200 unique cell types, which exist in various mammalian species. The major mechanism driving cellular differentiation and specification is differential gene expression regulation. Cis-acting enhancers and silencers appear to have key roles in regulating the expression of mammalian genes. However, these cis-acting elements are often located very far away from the regulated gene. Therefore, it is hard to find all of them and link them to the regulated gene. An intriguing and unresolved issue of the field is to identify all of the enhancers of a particular gene and link these short regulatory sequences to the genes they regulate and thus, reliably identify gene regulatory enhancer networks. Recent advances in molecular biological methods coupled with Next-Generation Sequencing (NGS) technologies have opened up new possibilities in this area of genomics. In this review we summarize the technological advances, bioinformatics challenges and the potential molecular mechanisms allowing the construction of enhancer networks operating in specific cell types and/or activated by various signals.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Egyetem tér 1., Debrecen H-4010, Hungary.
authors.forename: Bence
authors.initials: B
authors.lastname: Daniel
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Egyetem tér 1., Debrecen H-4010, Hungary.
authors.forename: Gergely
authors.initials: G
authors.lastname: Nagy
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Egyetem tér 1., Debrecen H-4010, Hungary; MTA-DE "Lendület" Immunogenomics Research Group, University of Debrecen, Egyetem tér 1., Debrecen, Hungary; Sanford-Burnham Medical Research Institute, 6400 Sanger Road, Orlando, FL 32827, USA. Electronic address: nagyl@med.unideb.hu.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Nagy
mesh_terms: D000818:Animals; D019295:Computational Biology / Q000379:methods*; D004742:Enhancer Elements, Genetic; D053263:Gene Regulatory Networks; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D017422:Sequence Analysis, DNA / Q000379:methods*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
keywords: Chromosome conformation; Cis-regulatory elements; Enhancers; Gene expression regulation; Genomic; Transcriptome