Identification of a Xist silencing domain by Tiling CRISPR.

Sci Rep 2019 Feb 20;9(1):2408. Epub 2019 Feb 20.

Tumor Initiation and Maintenance Program, NCI-designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA.

Despite essential roles played by long noncoding RNAs (lncRNAs) in development and disease, methods to determine lncRNA cis-elements are lacking. Here, we developed a screening method named "Tiling CRISPR" to identify lncRNA functional domains. Using this approach, we identified Xist A-Repeats as the silencing domain, an observation in agreement with published work, suggesting Tiling CRISPR feasibility. Mechanistic analysis suggested a novel function for Xist A-repeats in promoting Xist transcription. Overall, our method allows mapping of lncRNA functional domains in an unbiased and potentially high-throughput manner to facilitate the understanding of lncRNA functions.

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http://dx.doi.org/10.1038/s41598-018-36750-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382781PMC
February 2019

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References

(Supplied by CrossRef)

JL Rinn et al.
Cell 2007

J Zhao et al.
Science 2008

I Legnini et al.
Molecular cell 2014

AN Kallen et al.
Molecular cell 2013

Y Wang et al.
Dev Cell 2013

C Gong et al.
Nature 2011

CA McHugh et al.
Nature 2015

C Chu et al.
Cell 2015

L Cong et al.
Science 2013

M Jinek et al.
Science 2012

P Mali et al.
Science 2013

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