HES4 Lentiviral Activation Particles (h): sc-408938-LAC

HES4 (hairy and enhancer of split 4) is a basic helix–loop–helix transcriptional repressor that acts downstream of Notch signaling to modulate cell fate decisions, lineage commitment, and differentiation timing. By binding E-box–like motifs and recruiting corepressor complexes, HES4 helps constrain transcriptional programs linked to progenitor maintenance and developmental patterning. Altered HES family activity is commonly studied in contexts where Notch-regulated transcription affects proliferation, differentiation, and tissue homeostasis, including cancer biology and neurodevelopmental processes. In human systems, HES4 provides a tractable node for probing transcriptional circuitry at the interface of Notch pathway output and chromatin-regulated gene expression.

HES4 Lentiviral Activation Particles (h) address this need by packaging the complete synergistic activation mediator (SAM) transcriptional activation system into transduction-ready, high-titer lentiviral particles, enabling efficient HES4 upregulation across a broader range of human cell types.

HES4 Lentiviral Activation Particles (h) 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 HES4 transcriptional start site, where VP64, p65, and HSF1 act cooperatively to recruit endogenous transcriptional machinery and drive sustained upregulation of endogenous HES4 expression. The use of nuclease-inactive dCas9 avoids the introduction of double-strand DNA breaks and preserves the native HES4 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.