LXR beta/NER/NR1H2 CRISPR Activation Plasmid (h): sc-400691-ACT

NR1H2 encodes liver X receptor beta (LXRβ), a ligand-activated nuclear receptor that forms heterodimers with RXR to regulate transcriptional programs controlling cholesterol efflux, lipid homeostasis, and inflammatory signaling. LXRβ integrates sterol-sensing with metabolic gene expression, influencing pathways such as reverse cholesterol transport (including ABCA1/ABCG1 regulation), macrophage foam cell biology, and crosstalk with NF-κB–linked inflammatory responses. In human tissues and cell models, altered LXRβ activity has been associated with dysregulated lipid metabolism and inflammatory states relevant to atherosclerosis, metabolic dysfunction, and neuroinflammation, supporting mechanistic studies in immunometabolism and neurobiology.

LXR beta/NER/NR1H2 CRISPR Activation Plasmid (h) provides a targeted, non-destructive approach to upregulating endogenous NR1H2 expression without altering the underlying DNA sequence.

LXR beta/NER/NR1H2 CRISPR Activation Plasmid (h) is a three-plasmid synergistic activation mediator (SAM) system engineered for highly efficient, site-specific transcriptional upregulation of the NR1H2 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 NR1H2 transcriptional start site, where VP64, p65, and HSF1 act in concert to recruit transcriptional machinery and drive upregulation of endogenous LXR beta/NER/NR1H2 expression. Unlike nuclease-active Cas9, dCas9 does not introduce double-strand breaks or modify the genomic sequence, preserving the native NR1H2 locus and enabling the study of LXR beta/NER/NR1H2-dependent transcriptional responses at the endogenous locus, making it a valuable tool for functional studies, target gene identification, and the modeling of LXR beta/NER/NR1H2 pathway restoration in tumor cells with silenced or reduced NR1H2 expression.

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