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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]