HNF-3β Lentiviral Activation Particles (m): sc-420890-LAC

Foxa2 encodes hepatocyte nuclear factor 3 beta (HNF-3β), a forkhead box transcription factor that functions as a pioneer factor to open chromatin and coordinate lineage-specific gene programs during endoderm formation. In mouse development and adult tissues, HNF-3β regulates transcriptional networks controlling hepatic and pancreatic differentiation, bile acid and glucose metabolism, and epithelial homeostasis through interactions with nuclear receptor signaling and other transcriptional regulators. Foxa2 activity integrates developmental patterning cues and metabolic pathways, influencing cell identity decisions and stress responses. Dysregulation of Foxa2-associated programs has been linked to altered metabolic regulation and tissue remodeling phenotypes relevant to diabetes and liver disease models.

HNF-3β 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 Foxa2 upregulation across a broader range of human cell types.

HNF-3β 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 Foxa2 transcriptional start site, where VP64, p65, and HSF1 act cooperatively to recruit endogenous transcriptional machinery and drive sustained upregulation of endogenous HNF-3β expression. The use of nuclease-inactive dCas9 avoids the introduction of double-strand DNA breaks and preserves the native Foxa2 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.