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10.1038/nbt.3678 http://scihub22266oqcxt.onion/10.1038/nbt.3678 C5125825!5125825 !27701403     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=27701403 &cmd=llinks): Failed to open stream: HTTP request failed! 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Genome-scale high-resolution mapping of activating and repressive nucleotides in regulatory regions |pdf=|usr=}}{{27701403 }} gab.com Text Genome-scale high-resolution mapping of activating and repressive nucleotides in regulatory regions JO: Nat Biotechnol http://www.kidney.de/pget.php?&tw=1&pmid=27701403 #FOAvip Massively parallel reporter assays (MPRAs) enable nucleotide-resolution dissection of transcriptional regulatory regions, such as enhancers, but only few regions at a time. Here we present a combined experimental and computational approach, Systematic high-resolution activation and repression profiling with reporter tiling using MPRA (Sharpr-MPRA), that allows high-resolution analysis of thousands of regions simultaneously. Sharpr-MPRA combines dense tiling of overlapping MPRA constructs with a probabilistic graphical model to recognize functional regulatory nucleotides, and to distinguish activating and repressive nucleotides, using their inferred contribution to reporter gene expression. We used Sharpr-MPRA to test 4.6 million nucleotides spanning 15,000 putative regulatory regions tiled at 5-nucleotide resolution in two human cell types. Our results recovered known cell-type-specific regulatory motifs and evolutionarily conserved nucleotides, and distinguished known activating and repressive motifs. Our results also showed that endogenous chromatin state and DNA accessibility are both predictive of regulatory function in reporter assays, identified retroviral elements with activating roles, and uncovered 'attenuator' motifs with repressive roles in active chromatin. Twit Text FOAVip Genome-scale high-resolution mapping of activating and repressive nucleotides in regulatory regions ????Nat Biotechnol http://www.kidney.de/pget.php?&tw=1&pmid=27701403 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27701403 #FOAvip English Wikipedia <ref>{{Cite pmid|27701403 }}</ref> Genome-scale high-resolution mapping of activating and repressive nucleotides in regulatory regions #MMPMID27701403 Ernst J ; Melnikov A ; Zhang X ; Wang L ; Rogov P ; Mikkelsen TS ; Kellis M Nat Biotechnol 2016[Nov]; 34 (11 ): 1180-1190 PMID27701403 show ga Massively parallel reporter assays (MPRAs) enable nucleotide-resolution dissection of transcriptional regulatory regions, such as enhancers, but only few regions at a time. Here we present a combined experimental and computational approach, Systematic high-resolution activation and repression profiling with reporter tiling using MPRA (Sharpr-MPRA), that allows high-resolution analysis of thousands of regions simultaneously. Sharpr-MPRA combines dense tiling of overlapping MPRA constructs with a probabilistic graphical model to recognize functional regulatory nucleotides, and to distinguish activating and repressive nucleotides, using their inferred contribution to reporter gene expression. We used Sharpr-MPRA to test 4.6 million nucleotides spanning 15,000 putative regulatory regions tiled at 5-nucleotide resolution in two human cell types. Our results recovered known cell-type-specific regulatory motifs and evolutionarily conserved nucleotides, and distinguished known activating and repressive motifs. Our results also showed that endogenous chromatin state and DNA accessibility are both predictive of regulatory function in reporter assays, identified retroviral elements with activating roles, and uncovered 'attenuator' motifs with repressive roles in active chromatin. |Chromosome Mapping/*methods [MESH] |Conserved Sequence/genetics [MESH] |Epigenetic Repression/*genetics [MESH] |Genome, Human/*genetics [MESH] |High-Throughput Nucleotide Sequencing/*methods [MESH] |Humans [MESH] |Nucleotides/*genetics [MESH] |Regulatory Sequences, Nucleic Acid/*genetics [MESH] |Reproducibility of Results [MESH]Genome-scale high-resolution mapping of activating and repressive nucl(epmc).pdf DeepDyve Pubget Overpricing