Super-Enhancers at the Nanog Locus Differentially Regulate Neighboring Pluripotency-Associated Genes.

Autor:	Blinka S; Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53226, USA., Reimer MH Jr; Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53226, USA., Pulakanti K; Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53226, USA., Rao S; Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53226, USA; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Electronic address: sridhar.rao@bcw.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2016 Sep 27; Vol. 17 (1), pp. 19-28.
DOI:	10.1016/j.celrep.2016.09.002
Abstrakt:	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. (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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