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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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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 Jr ; Pulakanti K ; Rao S
  • Cell Rep 2016[Sep]; 17 (1 ): 19-28 PMID27681417 show 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 enhancer-derived RNAs (eRNAs). It remains unclear whether super-enhancers robustly activate genes in situ and whether their 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.
  • |*Enhancer Elements, Genetic [MESH]
  • |Animals [MESH]
  • |CRISPR-Cas Systems [MESH]
  • |Chromosomal Proteins, Non-Histone [MESH]
  • |Clustered Regularly Interspaced Short Palindromic Repeats [MESH]
  • |Endonucleases/genetics/metabolism [MESH]
  • |Gene Editing [MESH]
  • |Gene Expression Regulation [MESH]
  • |Human Embryonic Stem Cells/cytology/*metabolism [MESH]
  • |Humans [MESH]
  • |Mice [MESH]
  • |NIH 3T3 Cells [MESH]
  • |Nanog Homeobox Protein/*genetics/metabolism [MESH]
  • |Pluripotent Stem Cells/cytology/*metabolism [MESH]
  • |Primary Cell Culture [MESH]
  • |Proteins/*genetics/metabolism [MESH]
  • |RNA, Long Noncoding/*genetics/metabolism [MESH]


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