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Series GSE234491 Query DataSets for GSE234491
Status Public on Jun 09, 2023
Title Chem-CRISPR/dCas9FCPF - a platform for chemically induced epigenome editing
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Epigenetic aberration is one of the major driving factors in the initiation, promotion, and progression of human cancer and it is also often associated with acquired therapeutic resistance. Several chemical epigenetic modulators have been reported. However, results from animal models and clinical trials have indicated that severe on- and off-target toxicity is one of the leading factors behind failures in epidrug development. CRISPR/dCas9 technology provides a powerful tool for precise epigenetic regulation at the single-gene level. This approach requires ectopic expression of exogenous epigenetic modulatory proteins, which cause side effects and technical challenges for preparation and delivery. Recently, we have shown that Cas9 tagging with the peptide motif (FCPF) was recognized by perfluoro biphenyl derivatives. Here, we introduced the FCPF-tag into dCas9 and report a chemically induced platform for epigenome editing (Chem-CRISPR/dCas9FCPF). By conjugating JQ1, a BRD4 inhibitor, to perfluoro biphenyl (JQ1-FCPF), we demonstrate that JQ1-FCPF covalently binds to CRISPR/dCas9 and specifically inhibits BRD4 in proximity to the promoters/enhancers of c-MYC with the guidance of c-MYC sgRNAs. Thus, we achieved epigenetic modulation of c-MYC with high efficiency and specificity.
 
Overall design BRD4 ChIP-Seq experiment on K562 cells to study specificity of dCas9-based, chemical-mediated epigenome editing
 
Contributor(s) Sprang M, Andrade-Navarro MA, Cheng X
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Submission date Jun 08, 2023
Last update date Jun 11, 2023
Contact name Xinlai Cheng
E-mail(s) Cheng@pharmchem.uni-frankfurt.de
Organization name Goethe university Frankfurt
Department Pharmaceutical Chemistry
Street address Max-von-Laue-Strasse 15. R. 3.652
City Frankfurt
ZIP/Postal code D-60438
Country Germany
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (11)
GSM7469512 1a
GSM7469513 1b
GSM7469514 2a
Relations
BioProject PRJNA981533

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE234491_RAW.tar 1.6 Mb (http)(custom) TAR (of BED)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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