Synthetic transcription elongation factors license transcription across repressive chromatin.
Science
; 358(6370): 1617-1622, 2017 12 22.
Article
em En
| MEDLINE
| ID: mdl-29192133
ABSTRACT
The release of paused RNA polymerase II into productive elongation is highly regulated, especially at genes that affect human development and disease. To exert control over this rate-limiting step, we designed sequence-specific synthetic transcription elongation factors (Syn-TEFs). These molecules are composed of programmable DNA-binding ligands flexibly tethered to a small molecule that engages the transcription elongation machinery. By limiting activity to targeted loci, Syn-TEFs convert constituent modules from broad-spectrum inhibitors of transcription into gene-specific stimulators. Here we present Syn-TEF1, a molecule that actively enables transcription across repressive GAA repeats that silence frataxin expression in Friedreich's ataxia, a terminal neurodegenerative disease with no effective therapy. The modular design of Syn-TEF1 defines a general framework for developing a class of molecules that license transcription elongation at targeted genomic loci.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ataxia de Friedreich
/
Cromatina
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Ativação Transcricional
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Proteínas de Ligação ao Ferro
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Fatores de Elongação da Transcrição
Limite:
Humans
Idioma:
En
Revista:
Science
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos