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Nat Methods DOI:10.1038/s41592-021-01224-1

Augmenting and directing long-range CRISPR-mediated activation in human cells.

Publication TypeJournal Article
Year of Publication2021
AuthorsY Tak, E, Horng, JE, Perry, NT, Schultz, HT, Iyer, S, Yao, Q, Zou, LS, Aryee, MJ, Pinello, L, J Joung, K
JournalNat Methods
Date Published2021 Aug 05
ISSN1548-7105
Abstract

Epigenetic editing is an emerging technology that uses artificial transcription factors (aTFs) to regulate expression of a target gene. Although human genes can be robustly upregulated by targeting aTFs to promoters, the activation induced by directing aTFs to distal transcriptional enhancers is substantially less robust and consistent. Here we show that long-range activation using CRISPR-based aTFs in human cells can be made more efficient and reliable by concurrently targeting an aTF to the target gene promoter. We used this strategy to direct target gene choice for enhancers capable of regulating more than one promoter and to achieve allele-selective activation of human genes by targeting aTFs to single-nucleotide polymorphisms embedded in distally located sequences. Our results broaden the potential applications of the epigenetic editing toolbox for research and therapeutics.

DOI10.1038/s41592-021-01224-1
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/34354266?dopt=Abstract

Alternate JournalNat Methods
PubMed ID34354266
Grant ListR35 HG010717 / HG / NHGRI NIH HHS / United States
R01 CA211707 / CA / NCI NIH HHS / United States
R00 HG008399 / HG / NHGRI NIH HHS / United States
R35 GM118158 / GM / NIGMS NIH HHS / United States
R01 CA204954 / CA / NCI NIH HHS / United States