CBP/KAT3A/CREBBP CRISPR Activation Plasmid (h): sc-400200-ACT

CREBBP encodes CREB-binding protein (CBP/KAT3A), a transcriptional coactivator and lysine acetyltransferase that acetylates histones and non-histone substrates to modulate chromatin accessibility and gene expression. CBP integrates signals from CREB, nuclear receptors, and developmental transcription factors, coordinating programs involved in cell-cycle control, DNA damage responses, differentiation, and neuronal plasticity. Through its roles in enhancer function and transcriptional elongation, CBP participates in pathways such as cAMP/CREB signaling and broader epigenetic regulation of lineage-specific transcription. Altered CREBBP activity or dosage is linked to neurodevelopmental phenotypes and is recurrently implicated in cancer-associated transcriptional and chromatin dysregulation.

CBP/KAT3A/CREBBP CRISPR Activation Plasmid (h) provides a targeted, non-destructive approach to upregulating endogenous CREBBP expression without altering the underlying DNA sequence.

CBP/KAT3A/CREBBP CRISPR Activation Plasmid (h) is a three-plasmid synergistic activation mediator (SAM) system engineered for highly efficient, site-specific transcriptional upregulation of the CREBBP 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 CREBBP transcriptional start site, where VP64, p65, and HSF1 act in concert to recruit transcriptional machinery and drive upregulation of endogenous CBP/KAT3A/CREBBP expression. Unlike nuclease-active Cas9, dCas9 does not introduce double-strand breaks or modify the genomic sequence, preserving the native CREBBP locus and enabling the study of CBP/KAT3A/CREBBP-dependent transcriptional responses at the endogenous locus, making it a valuable tool for functional studies, target gene identification, and the modeling of CBP/KAT3A/CREBBP pathway restoration in tumor cells with silenced or reduced CREBBP expression.

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