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- W3201302222 endingPage "1394" @default.
- W3201302222 startingPage "1383" @default.
- W3201302222 abstract "Enhancers generate bidirectional noncoding enhancer RNAs (eRNAs) that may regulate gene expression. At present, the eRNA function remains enigmatic. Here, we report a 5' capped antisense eRNA PEARL (Pcdh eRNA associated with R-loop formation) that is transcribed from the protocadherin (Pcdh) α HS5-1 enhancer region. Through loss- and gain-of-function experiments with CRISPR/Cas9 DNA fragment editing, CRISPRi, and CRISPRa, as well as locked nucleic acid strategies, in conjunction with ChIRP, MeDIP, DRIP, QHR-4C, and HiChIP experiments, we found that PEARL regulates Pcdhα gene expression by forming local RNA-DNA duplexes (R-loops) in situ within the HS5-1 enhancer region to promote long-distance chromatin interactions between distal enhancers and target promoters. In particular, increased levels of eRNA PEARL via perturbing transcription elongation factor SPT6 lead to strengthened local three-dimensional chromatin organization within the Pcdh superTAD. These findings have important implications regarding molecular mechanisms by which the HS5-1 enhancer regulates stochastic Pcdhα promoter choice in single cells in the brain." @default.
- W3201302222 created "2021-09-27" @default.
- W3201302222 creator A5030161456 @default.
- W3201302222 creator A5062791337 @default.
- W3201302222 creator A5068836221 @default.
- W3201302222 creator A5073525246 @default.
- W3201302222 date "2021-09-16" @default.
- W3201302222 modified "2023-10-17" @default.
- W3201302222 title "Systematic functional characterization of antisense eRNA of protocadherin <i>α</i> composite enhancer" @default.
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- W3201302222 doi "https://doi.org/10.1101/gad.348621.121" @default.
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- W3201302222 hasPublicationYear "2021" @default.
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