Augmenting and directing long-range CRISPR-mediated activation in human cells.
Nat Methods
; 18(9): 1075-1081, 2021 09.
Article
en En
| MEDLINE
| ID: mdl-34354266
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Regiones Promotoras Genéticas
/
Marcación de Gen
/
Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas
Límite:
Humans
Idioma:
En
Revista:
Nat Methods
Asunto de la revista:
TECNICAS E PROCEDIMENTOS DE LABORATORIO
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos