HNF-4α Lentiviral Activation Particles (m): sc-420892-LAC

Hnf4a encodes hepatocyte nuclear factor 4 alpha (HNF-4α), a nuclear receptor transcription factor that controls gene networks required for hepatocyte differentiation, epithelial polarity, and metabolic homeostasis. In mouse tissues, HNF-4α coordinates pathways governing gluconeogenesis, lipid transport, bile acid metabolism, and xenobiotic detoxification through direct regulation of liver-enriched and intestinal epithelial gene programs. Perturbation of HNF-4α activity disrupts transcriptional control of transporters and metabolic enzymes, impacting insulin and nutrient-responsive signaling and epithelial barrier functions. Consequently, Hnf4a is widely studied in models of metabolic dysfunction, inflammatory injury, and liver and intestinal pathophysiology where transcriptional rewiring drives phenotype.

HNF-4α Lentiviral Activation Particles (m) address this need by packaging the complete synergistic activation mediator (SAM) transcriptional activation system into transduction-ready, high-titer lentiviral particles, enabling efficient Hnf4a upregulation across a broader range of human cell types.

HNF-4α Lentiviral Activation Particles (m) 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 Hnf4a transcriptional start site, where VP64, p65, and HSF1 act cooperatively to recruit endogenous transcriptional machinery and drive sustained upregulation of endogenous HNF-4α expression. The use of nuclease-inactive dCas9 avoids the introduction of double-strand DNA breaks and preserves the native Hnf4a 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.