Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Egyetem tér 1., Debrecen H-4010, Hungary.
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.
FEBS Lett. 2014 Aug 1;588(15):2379-91. doi: 10.1016/j.febslet.2014.05.041. Epub 2014 Jun 16.
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.
基因组中编码的信息支持了 200 多种独特细胞类型的分化和功能，这些细胞类型存在于各种哺乳动物物种中。推动细胞分化和特化的主要机制是差异基因表达调控。顺式作用增强子和沉默子似乎在调节哺乳动物基因的表达中起着关键作用。然而，这些顺式作用元件通常位于被调控基因的很远的地方。因此，很难找到所有这些元件，并将它们与被调控的基因联系起来。该领域一个有趣且尚未解决的问题是识别特定基因的所有增强子，并将这些短的调控序列与它们所调控的基因联系起来，从而可靠地识别基因调控增强子网络。分子生物学方法的最新进展以及下一代测序 (NGS) 技术在基因组学的这一领域开辟了新的可能性。在这篇综述中，我们总结了技术进步、生物信息学挑战以及潜在的分子机制，这些机制允许构建在特定细胞类型中起作用和/或被各种信号激活的增强子网络。
