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10.1186/s13059-020-01984-7 http://scihub22266oqcxt.onion/10.1186/s13059-020-01984-7 32293525!7087399!32293525     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=32293525&cmd=llinks): Failed to open stream: HTTP request failed! 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Tandem CTCF sites function as insulators to balance spatial chromatin contacts and topological enhancer-promoter selection |pdf=|usr=}}{{32293525}} gab.com Text Tandem CTCF sites function as insulators to balance spatial chromatin contacts and topological enhancer-promoter selection JO: Genome Biol http://www.kidney.de/pget.php?&tw=1&pmid=32293525 #FOAvip BACKGROUND: CTCF is a key insulator-binding protein, and mammalian genomes contain numerous CTCF sites, many of which are organized in tandem. RESULTS: Using CRISPR DNA-fragment editing, in conjunction with chromosome conformation capture, we find that CTCF sites, if located between enhancers and promoters in the protocadherin (Pcdh) and beta-globin clusters, function as an enhancer-blocking insulator by forming distinct directional chromatin loops, regardless whether enhancers contain CTCF sites or not. Moreover, computational simulation in silico and genetic deletions in vivo as well as dCas9 blocking in vitro revealed balanced promoter usage in cell populations and stochastic monoallelic expression in single cells by large arrays of tandem CTCF sites in the Pcdh and immunoglobulin heavy chain (Igh) clusters. Furthermore, CTCF insulators promote, counter-intuitively, long-range chromatin interactions with distal directional CTCF sites, consistent with the cohesin "loop extrusion" model. Finally, gene expression levels are negatively correlated with CTCF insulators located between enhancers and promoters on a genome-wide scale. Thus, single CTCF insulators ensure proper enhancer insulation and promoter activation while tandem CTCF topological insulators determine balanced spatial contacts and promoter choice. CONCLUSIONS: These findings have interesting implications on the role of topological chromatin insulators in 3D genome folding and developmental gene regulation. Twit Text FOAVip Tandem CTCF sites function as insulators to balance spatial chromatin contacts and topological enhancer-promoter selection ????Genome Biol http://www.kidney.de/pget.php?&tw=1&pmid=32293525 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32293525 #FOAvip English Wikipedia <ref>{{Cite pmid|32293525}}</ref> Tandem CTCF sites function as insulators to balance spatial chromatin contacts and topological enhancer-promoter selection #MMPMID32293525 Jia Z; Li J; Ge X; Wu Y; Guo Y; Wu Q Genome Biol 2020[Mar]; 21 (1): 75 PMID32293525show ga BACKGROUND: CTCF is a key insulator-binding protein, and mammalian genomes contain numerous CTCF sites, many of which are organized in tandem. RESULTS: Using CRISPR DNA-fragment editing, in conjunction with chromosome conformation capture, we find that CTCF sites, if located between enhancers and promoters in the protocadherin (Pcdh) and beta-globin clusters, function as an enhancer-blocking insulator by forming distinct directional chromatin loops, regardless whether enhancers contain CTCF sites or not. Moreover, computational simulation in silico and genetic deletions in vivo as well as dCas9 blocking in vitro revealed balanced promoter usage in cell populations and stochastic monoallelic expression in single cells by large arrays of tandem CTCF sites in the Pcdh and immunoglobulin heavy chain (Igh) clusters. Furthermore, CTCF insulators promote, counter-intuitively, long-range chromatin interactions with distal directional CTCF sites, consistent with the cohesin "loop extrusion" model. Finally, gene expression levels are negatively correlated with CTCF insulators located between enhancers and promoters on a genome-wide scale. Thus, single CTCF insulators ensure proper enhancer insulation and promoter activation while tandem CTCF topological insulators determine balanced spatial contacts and promoter choice. CONCLUSIONS: These findings have interesting implications on the role of topological chromatin insulators in 3D genome folding and developmental gene regulation. |*Enhancer Elements, Genetic[MESH] |*Insulator Elements[MESH] |*Promoter Regions, Genetic[MESH] |Binding Sites[MESH] |CCCTC-Binding Factor/*metabolism[MESH] |Cadherin Related Proteins[MESH] |Cadherins/genetics[MESH] |Chromatin/chemistry[MESH]Tandem CTCF sites function as insulators to balance spatial chromatin (epmc).pdf DeepDyve Pubget Overpricing