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Series GSE232132 Query DataSets for GSE232132
Status Public on Jun 09, 2023
Title Chem-CRISPR/dCas9 -a chemically induced platform for epigenome editing
Organism Homo sapiens
Experiment type Expression 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 Analysis of gene expression upon various treatments
Total RNA obtained from isolated K562 cells after 1 h treatment, including DMSO as control, JQ1 -sgRNA, JQ1 +sgRNA, JQ1-FCPF -sgRNA, JQ1-FCPF +sgRNA
Contributor(s) Cheng X
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Submission date May 10, 2023
Last update date Jun 11, 2023
Contact name Xinlai Cheng
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)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (15)
GSM7316129 X6a
GSM7316130 X6b
GSM7316131 X6c
BioProject PRJNA971100

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
GSE232132_Normalized_Counts_GEO.xlsx 2.5 Mb (ftp)(http) XLSX
GSE232132_RAW.tar 65.0 Mb (http)(custom) TAR (of TXT)
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Raw data are available in SRA
Processed data are available on Series record

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