Dataset Information

EnhancerDB: a resource of transcriptional regulation in the context of enhancers.

ABSTRACT: Enhancers can act as cis-regulatory elements to control transcriptional regulation by recruiting DNA-binding transcription factors (TFs) in a tissue-specific manner. Recent studies show that enhancers regulate not only protein-coding genes but also microRNAs (miRNAs), and mutations within the TF binding sites (TFBSs) located on enhancers will cause a variety of diseases such as cancer. However, a comprehensive resource to integrate these regulation elements for revealing transcriptional regulations in the context of enhancers is not currently available. Here, we introduce EnhancerDB, a web-accessible database to provide a resource to browse and search regulatory relationships identified in this study, including 131 054 581 TF-enhancer, 17 059 enhancer-miRNAs, 318 993 enhancer-genes, 4 639 558 TF-miRNAs, 1 059 695 TF-genes, 11 439 394 enhancer-single-nucleotide polymorphisms (SNPs) and 23 334 genes associated with expression quantitative trait loci (eQTL) SNP and expression profile of TF/gene/miRNA across multiple human tissues/cell lines. We also developed a tool that further allows users to define tissue-specific enhancers by setting the threshold score of tissue specificity of enhancers. In addition, links to external resources are also available at EnhancerDB.

SUBMITTER: Kang R

PROVIDER: S-EPMC6344666 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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EnhancerDB: a resource of transcriptional regulation in the context of enhancers.

Kang Ran R Zhang Yiming Y Huang Qingqing Q Meng Junhua J Ding Ruofan R Chang Yunjian Y Xiong Lili L Guo Zhiyun Z

Database : the journal of biological databases and curation 20190101

Enhancers can act as cis-regulatory elements to control transcriptional regulation by recruiting DNA-binding transcription factors (TFs) in a tissue-specific manner. Recent studies show that enhancers regulate not only protein-coding genes but also microRNAs (miRNAs), and mutations within the TF binding sites (TFBSs) located on enhancers will cause a variety of diseases such as cancer. However, a comprehensive resource to integrate these regulation elements for revealing transcriptional regulati ...[more]

PMID: 30689845

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Project description:The chondroitin sulfate proteoglycan core protein aggrecan is the major protein constituent of cartilage aside from collagen, and is largely responsible for its distinctive mechanical properties. Aggrecan is required both for proper cartilage formation in development and maintenance of mature cartilage. Prominent ACAN transcription is a conserved feature of vertebrate cartilage, although little is known about its specific transcriptional regulation. We examined the genomic interval containing human ACAN for transcriptional enhancers directing expression to cartilage, using a functional assay in transgenic zebrafish. We tested 24 conserved non-coding sequences, representing ~6% of the total sequence in the interval, and identified eleven independently capable of regulating reporter gene expression in cartilage. These enhancers were widely spaced, from >100kb upstream of the gene to within the first intron. While the majority displayed broad cartilage expression in zebrafish larvae, several were restricted to a subset of cartilage cells in the craniofacial skeleton. In older fish, the enhancers displayed differential activity; some maintained expression, either in all cartilage or preferentially in articular cartilage at the joints, while others were not active. This remarkable degree of overlapping regulatory control has been highly conserved; we identified clear orthologues of six enhancers at the chicken ACAN locus, arranged in the same order relative to the gene. These were also functional in directing expression to cartilage in transgenic zebrafish. Several enhancers contain potential binding sites for Sox9, consistent with its described role as an upstream regulator of ACAN expression. However, others lacked Sox9 consensus binding sites, implicating additional pathways and transcription factors as regulators of ACAN expression in cartilage, either in development or adult tissue. Our identification of these enhancer sequences is the necessary first step in detailed examination of the upstream regulators of ACAN expression.

Dataset Information

EnhancerDB: a resource of transcriptional regulation in the context of enhancers.

Publications

EnhancerDB: a resource of transcriptional regulation in the context of enhancers.

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