TEL CRISPR Activation Plasmid (h): sc-402207-ACT

ETV6 (TEL) is an ETS family transcriptional repressor essential for hematopoietic stem and progenitor cell homeostasis, lineage commitment, and maintenance of genomic stability. Through its PNT oligomerization domain and ETS DNA-binding domain, TEL coordinates transcriptional programs that shape cell-cycle control, differentiation, and survival pathways, including regulation of cytokine-responsive signaling networks. Disruption of ETV6 function is strongly associated with hematologic disease biology, most notably via recurrent gene fusions and loss-of-function lesions that alter transcriptional regulation and chromatin state. These features make TEL a widely studied node for investigating oncogenic transcriptional rewiring, clonal evolution, and mechanisms of blood cell development.

TEL CRISPR Activation Plasmid (h) provides a targeted, non-destructive approach to upregulating endogenous ETV6 expression without altering the underlying DNA sequence.

TEL CRISPR Activation Plasmid (h) is a three-plasmid synergistic activation mediator (SAM) system engineered for highly efficient, site-specific transcriptional upregulation of the ETV6 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 ETV6 transcriptional start site, where VP64, p65, and HSF1 act in concert to recruit transcriptional machinery and drive upregulation of endogenous TEL expression. Unlike nuclease-active Cas9, dCas9 does not introduce double-strand breaks or modify the genomic sequence, preserving the native ETV6 locus and enabling the study of TEL-dependent transcriptional responses at the endogenous locus, making it a valuable tool for functional studies, target gene identification, and the modeling of TEL pathway restoration in tumor cells with silenced or reduced ETV6 expression.

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