Browsing by keyword "Enhancer"
Now showing items 1-3 of 3
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A curated benchmark of enhancer-gene interactions for evaluating enhancer-target gene prediction methodsBACKGROUND: Many genome-wide collections of candidate cis-regulatory elements (cCREs) have been defined using genomic and epigenomic data, but it remains a major challenge to connect these elements to their target genes. RESULTS: To facilitate the development of computational methods for predicting target genes, we develop a Benchmark of candidate Enhancer-Gene Interactions (BENGI) by integrating the recently developed Registry of cCREs with experimentally derived genomic interactions. We use BENGI to test several published computational methods for linking enhancers with genes, including signal correlation and the TargetFinder and PEP supervised learning methods. We find that while TargetFinder is the best-performing method, it is only modestly better than a baseline distance method for most benchmark datasets when trained and tested with the same cell type and that TargetFinder often does not outperform the distance method when applied across cell types. CONCLUSIONS: Our results suggest that current computational methods need to be improved and that BENGI presents a useful framework for method development and testing.
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Combinatorial action of NF-Y and TALE at embryonic enhancers defines distinct gene expression programs during zygotic genome activation in zebrafishAnimal embryogenesis is initiated by maternal factors, but zygotic genome activation (ZGA) shifts regulatory control to the embryo during blastula stages. ZGA is thought to be mediated by maternally provided transcription factors (TFs), but few such TFs have been identified in vertebrates. Here we report that NF-Y and TALE TFs bind zebrafish genomic elements associated with developmental control genes already at ZGA. In particular, co-regulation by NF-Y and TALE is associated with broadly acting genes involved in transcriptional control, while regulation by either NF-Y or TALE defines genes in specific developmental processes, such that NF-Y controls a cilia gene expression program while TALE controls expression of hox genes. We also demonstrate that NF-Y and TALE-occupied genomic elements function as enhancers during embryogenesis. We conclude that combinatorial use of NF-Y and TALE at developmental enhancers permits the establishment of distinct gene expression programs at zebrafish ZGA.
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PSF contacts exon 7 of SMN2 pre-mRNA to promote exon 7 inclusionSpinal muscular atrophy (SMA) is an autosomal recessive genetic disease and a leading cause of infant mortality. Deletions or mutations in SMN1, a gene that encodes an SMN protein, which regulates assembly/disassembly of U snRNP and is suggested to direct axonal transport of beta-actin mRNA in neurons, are responsible for most cases of SMA disease. However, humans contain a second SMN gene called SMN2. Unlike SMN1, the majority of SMN2 mRNA don't include exon 7. Here we show that increased expression of PSF significantly promotes inclusion of exon 7 in the SMN2 and SMN1 mRNA, whereas reduced expression of PSF promotes exon 7 skipping in various cell lines and in fibroblast cells from SMA patients. In addition, we present evidence showing that PSF interacts with the GAAGGA enhancer in exon 7. We also demonstrate that a mutation in this enhancer abolishes the effects of PSF on exon 7 splicing. Furthermore we show that the RNA target sequences of PSF and tra2beta in exon 7 are partially overlapped. These results lead us to conclude that PSF interacts with an enhancer in exon 7 to promote exon 7 splicing of SMN2 pre-mRNA.
