CoREST CRISPR Activation Plasmid (h): sc-402066-ACT

RCOR1 encodes CoREST, a core transcriptional co-repressor that scaffolds chromatin-modifying complexes containing REST, HDAC1/2, and LSD1/KDM1A to regulate promoter-proximal histone acetylation and H3K4 methylation states. Through these interactions, CoREST coordinates epigenetic control of neuronal gene programs, differentiation, and maintenance of cell identity, while also influencing cell-cycle and stress-responsive transcriptional networks. Dysregulated RCOR1/CoREST activity has been implicated in aberrant chromatin repression programs observed across neurodevelopmental and neurodegenerative contexts and in cancers where epigenetic remodeling supports altered lineage states. As a nodal regulator of transcriptional repression, RCOR1 is commonly studied in pathways linking chromatin architecture to gene expression plasticity.

CoREST CRISPR Activation Plasmid (h) provides a targeted, non-destructive approach to upregulating endogenous RCOR1 expression without altering the underlying DNA sequence.

CoREST CRISPR Activation Plasmid (h) is a three-plasmid synergistic activation mediator (SAM) system engineered for highly efficient, site-specific transcriptional upregulation of the RCOR1 locus in human cell lines. The system is built around a catalytically inactive Cas9 (dCas9) carrying two inactivating mutations (D10A and N863A) that eliminate nuclease activity while preserving DNA binding. This dCas9 is fused to VP64, a potent transcriptional activator, and is co-expressed with a blasticidin resistance gene for selection. The second plasmid encodes the MS2-p65-HSF1 fusion protein, a secondary activator complex that works in concert with dCas9-VP64, alongside a hygromycin resistance gene. The third plasmid encodes a target-specific 20 nt sgRNA fused to two MS2 RNA aptamers that recruit the MS2-p65-HSF1 complex to the activation site, accompanied by a puromycin resistance gene. The three plasmids are delivered at a 1:1:1 mass ratio for balanced expression of all system components.

Once assembled at the target locus, the SAM complex binds within approximately 200 bp upstream of the RCOR1 transcriptional start site, where VP64, p65, and HSF1 act in concert to recruit transcriptional machinery and drive upregulation of endogenous CoREST expression. Unlike nuclease-active Cas9, dCas9 does not introduce double-strand breaks or modify the genomic sequence, preserving the native RCOR1 locus and enabling the study of CoREST-dependent transcriptional responses at the endogenous locus, making it a valuable tool for functional studies, target gene identification, and the modeling of CoREST pathway restoration in tumor cells with silenced or reduced RCOR1 expression.

For Research Use Only. Not Intended for Diagnostic or Therapeutic Use.