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10.1016/j.celrep.2016.09.002

http://scihub22266oqcxt.onion/10.1016/j.celrep.2016.09.002
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C5111363!5111363!27681417
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suck abstract from ncbi


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pmid27681417      Cell+Rep 2016 ; 17 (1): 19-28
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  • Super-Enhancers at the Nanog Locus Differentially Regulate Neighboring Pluripotency-Associated Genes #MMPMID27681417
  • Blinka S; Reimer MH; Pulakanti K; Rao S
  • Cell Rep 2016[Sep]; 17 (1): 19-28 PMID27681417show ga
  • Super-enhancers are tissue specific cis-regulatory elements that drive expression of genes associated with cell identity and malignancy. A cardinal feature of super-enhancers is that they are transcribed to produce long non-coding RNAs (eRNAs). It remains unclear whether epigenetically indistinguishable super-enhancers robustly activate genes in situ and if these functions are attributable to eRNAs or the DNA element. CRISPR/Cas9 was used to systematically delete three discrete super-enhancers at the Nanog locus in embryonic stem cells, revealing functional differences in Nanog transcriptional regulation. One distal super-enhancer 45 kb upstream of Nanog (?45 enhancer) regulates both nearest neighbor genes Nanog and Dppa3. Interestingly, eRNAs produced at the ?45 enhancer specifically regulate Dppa3 expression by stabilizing looping of the ?45 enhancer and Dppa3. Our work illustrates that genomic editing is required to determine enhancer function and points to a method to selectively target a subset of super-enhancer regulated genes by depleting eRNAs.
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