PXD048673

PXD048673 is an original dataset announced via ProteomeXchange.

Title	Chem-CRISPR/dCas9FCPF - A platform for chemically induced epigenome editing
Description	Epigenetic 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.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_12:39:51.284.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Frank Stein
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-18 01:48:10	ID requested
⏵ 1	2025-05-06 12:39:52	announced

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]

submitter keyword: chemical epigenetic modulators,CRISPR/dCas9, gene therapy, Epigenome editing

Xinlai Cheng
contact affiliation	Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt am Main, Germany
contact email	Cheng@pharmchem.uni-frankfurt.de
lab head
Frank Stein
contact affiliation	EMBL
contact email	frank.stein@embl.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD048673

PRIDE project URI

• PRIDE
  1. PXD048673
     1. Label: PRIDE project
     2. Name: Chem-CRISPR/dCas9FCPF - A platform for chemically induced epigenome editing