Rev-erbα Lentiviral Activation Particles (h2): sc-401211-LAC-2

Human NR1D1 encodes the nuclear receptor Rev-erbα (NR1D1), a heme-binding transcriptional repressor that links cellular metabolism to circadian timing by modulating gene expression at Rev-erb/ROR response elements. Rev-erbα functions within the core clock circuitry to constrain BMAL1/CLOCK-driven transcription and coordinates pathways controlling lipid and glucose metabolism, mitochondrial function, and inflammatory signaling through interactions with corepressors such as NCoR/HDAC3. Dysregulation of NR1D1 has been associated with altered circadian rhythmicity and metabolic phenotypes, with reported relevance to cardiometabolic and inflammatory disease biology. Genome editing or perturbation of NR1D1 is therefore useful for dissecting transcriptional networks underlying circadian regulation, metabolic homeostasis, and immune-metabolic crosstalk in human cell models.

Rev-erbα Lentiviral Activation Particles (h2) address this need by packaging the complete synergistic activation mediator (SAM) transcriptional activation system into transduction-ready, high-titer lentiviral particles, enabling efficient NR1D1 upregulation across a broader range of human cell types.

Rev-erbα Lentiviral Activation Particles (h2) deliver all functional components of the synergistic activation mediator (SAM) system via lentiviral transduction. The system comprises three particle preparations co-transduced into target cells: one encoding catalytically inactive dCas9 (D10A and N863A mutations) fused to the VP64 transactivation domain with a blasticidin resistance gene; one encoding the MS2-p65-HSF1 fusion protein with a hygromycin resistance gene; and one encoding a target-specific 20 nt sgRNA fused to two MS2 RNA aptamers with a puromycin resistance gene. Following lentiviral transduction and genomic integration of the expression cassettes, the SAM components are stably expressed and assemble at the target locus within the proximal promoter region upstream of the NR1D1 transcriptional start site, where VP64, p65, and HSF1 act cooperatively to recruit endogenous transcriptional machinery and drive sustained upregulation of endogenous Rev-erbα expression. The use of nuclease-inactive dCas9 avoids the introduction of double-strand DNA breaks and preserves the native NR1D1 genomic locus and regulatory architecture.

The lentiviral format offers several practical advantages: stable genomic integration supports heritable activation across cell divisions; high-titer particle preparations eliminate the need for in-house viral production; and compatibility with primary, non-dividing, and transfection-resistant cell types expands experimental accessibility. Successful transduction can be confirmed and enriched through triple antibiotic selection using puromycin, hygromycin, and blasticidin.

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