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PXD048673

PXD048673 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleChem-CRISPR/dCas9FCPF - A platform for chemically induced epigenome editing
DescriptionEpigenetic aberration is one of the major driving factors in human cancer, often leading to acquired resistance to chemotherapies. Various chemical epigenetic modulators have been reported. Nonetheless, outcomes from animal models and clinical trials have underscored the substantial setbacks attributed to pronounced on- and off-target toxicities. To address these challenges, CRISPR/dCas9 technology emerges as a potent tool for precise epigenetic regulation. This relies on the co-expression of exogenous epigenetic modulator proteins, presenting technical challenges during preparation and delivery, as well as potential undesirable side effects. Recently, our research demonstrated that Cas9 tagged with the FCPF-peptide motif could be recognized by perfluoro biphenyl (PFB) derivatives. Here, we integrated the FCPF-tag into dCas9 and established a chemically inducible platform for epigenome editing, called Chem-CRISPR/dCas9FCPF. We designed a series of chemical inhibitor-PFB conjugates targeting various epigenetic modulator proteins. Focusing on JQ1, a BRD4 inhibitor, we demonstrate that c-MYC-sgRNA-guided JQ1-PFB specifically inhibits BRD4 in close proximity to the c-MYC promoter/enhancer, thereby effectively repressing the intricate transcription networks orchestrated by c-MYC. In conclusion, our Chem-CRISPR/dCas9FCPF platform presents a promising alternative to conventional fusion protein systems. It replaces exogenous epigenetic modulator proteins with chemical inhibitors, offering a highly efficient and precise approach to epigenome editing.
HostingRepositoryPRIDE
AnnounceDate2025-05-06
AnnouncementXMLSubmission_2025-05-06_12:39:51.284.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterFrank Stein
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-01-18 01:48:10ID requested
12025-05-06 12:39:52announced
Publication List
10.1093/nar/gkae798;
Altinbay M, Wang J, Chen J, Sch, ä, fer D, Sprang M, Blagojevic B, W, ö, lfl S, Andrade-Navarro MA, Dikic I, Knapp S, Cheng X, Chem-CRISPR/dCas9FCPF: a platform for chemically induced epigenome editing. Nucleic Acids Res, 52(19):11587-11601(2024) [pubmed]
Keyword List
submitter keyword: chemical epigenetic modulators,CRISPR/dCas9, gene therapy, Epigenome editing
Contact List
Xinlai Cheng
contact affiliationBuchmann Institute for Molecular Life Sciences, Goethe University Frankfurt am Main, Germany
contact emailCheng@pharmchem.uni-frankfurt.de
lab head
Frank Stein
contact affiliationEMBL
contact emailfrank.stein@embl.de
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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