Progesterone Receptor CRISPR Activation Plasmid (h): sc-400198-ACT

PGR encodes the human progesterone receptor, a ligand-activated nuclear hormone receptor that functions as a transcription factor to coordinate progesterone-dependent gene programs. Upon hormone binding, PGR regulates chromatin accessibility and transcriptional networks governing reproductive tissue development, cell cycle progression, differentiation, and inflammatory signaling through cross-talk with steroid receptor co-regulators and MAPK/PI3K pathways. Isoform-specific activity (PR-A and PR-B) shapes context-dependent responses in endometrium, breast, and ovary, influencing epithelial–stromal communication and hormone responsiveness. Dysregulated PGR signaling and altered receptor expression are commonly studied in hormone-responsive cancers and reproductive disorders, where it affects proliferation, invasion, and endocrine resistance mechanisms.

Progesterone Receptor CRISPR Activation Plasmid (h) provides a targeted, non-destructive approach to upregulating endogenous PGR expression without altering the underlying DNA sequence.

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

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