دورية أكاديمية
Dose-dependent activation of gene expression is achieved using CRISPR and small molecules that recruit endogenous chromatin machinery
| العنوان: | Dose-dependent activation of gene expression is achieved using CRISPR and small molecules that recruit endogenous chromatin machinery |
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| المؤلفون: | Chiarella, A.M., Butler, K.V., Gryder, B.E., Lu, D., Wang, T.A., Yu, X., Pomella, S., Khan, J., Jin, J., Hathaway, N.A. |
| المصدر: | Nature Biotechnology, 38(1) |
| بيانات النشر: | Nature Research |
| سنة النشر: | 2020 |
| المجموعة: | Carolina Digital Repository (UNC - University of North Carolina) |
| مصطلحات موضوعية: | Chromatin, Time Factors, Humans, Gene Expression Regulation, RNA, Guide, Cell Cycle Proteins, CRISPR-Cas Systems, Genome, Human, Transcription Factors, HEK293 Cells, Epigenesis, Genetic |
| الوصف: | Gene expression can be activated or suppressed using CRISPR–Cas9 systems. However, tools that enable dose-dependent activation of gene expression without the use of exogenous transcription regulatory proteins are lacking. Here we describe chemical epigenetic modifiers (CEMs) designed to activate the expression of target genes by recruiting components of the endogenous chromatin-activating machinery, eliminating the need for exogenous transcriptional activators. The system has two parts: catalytically inactive Cas9 (dCas9) in complex with FK506-binding protein (FKBP) and a CEM consisting of FK506 linked to a molecule that interacts with cellular epigenetic machinery. We show that CEMs upregulate gene expression at target endogenous loci up to 20-fold or more depending on the gene. We also demonstrate dose-dependent control of transcriptional activation, function across multiple diverse genes, reversibility of CEM activity and specificity of our best-in-class CEM across the genome. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.17615/z6bs-z243Test; https://cdr.lib.unc.edu/downloads/j6731d275?file=thumbnailTest; https://cdr.lib.unc.edu/downloads/j6731d275Test |
| DOI: | 10.17615/z6bs-z243 |
| الإتاحة: | https://doi.org/10.17615/z6bs-z243Test https://cdr.lib.unc.edu/downloads/j6731d275?file=thumbnailTest https://cdr.lib.unc.edu/downloads/j6731d275Test |
| حقوق: | http://rightsstatements.org/vocab/InC/1.0Test/ |
| رقم الانضمام: | edsbas.616D5B7F |
| قاعدة البيانات: | BASE |
| DOI: | 10.17615/z6bs-z243 |
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