Details

Autor(en) / Beteiligte

• Erwin, Graham S.
• Grieshop, Matthew P.
• Ali, Asfa
• Qi, Jun
• Lawlor, Matthew
• Kumar, Deepak
• Ahmad, Istaq
• McNally, Anna
• Teider, Natalia
• Worringer, Katie
• Sivasankaran, Rajeev
• Syed, Deeba N.
• Eguchi, Asuka
• Ashraf, Md
• Jeffery, Justin
• Xu, Mousheng
• Park, Paul M. C.
• Mukhtar, Hasan
• Srivastava, Achal K.
• Faruq, Mohammed
• Bradner, James E.
• Ansari, Aseem Z.

Titel

Synthetic transcription elongation factors license transcription across repressive chromatin

Ist Teil von

• Science (American Association for the Advancement of Science), 2017-12, Vol.358 (6370), p.1617-1622

Ort / Verlag

United States: American Association for the Advancement of Science

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.