Ascent Research’s DNTTIP1 Knockout K-562 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the K-562 chronic myelogenous leukemia cell line. This product offers a heterogeneous pool of cells carrying targeted disruptions in the DNTTIP1 gene, enabling loss-of-function studies without clonal selection. The knockout model facilitates investigation of DNTTIP1’s role in DNA repair, transcriptional regulation, and hematopoietic biology. The polyclonal format ensures representation of diverse knockout genotypes for robust phenotypic analyses.
The K-562 host cell line, derived from a CML patient in blast crisis, is a widely used model for leukemia and hematopoietic differentiation. K-562 cells can undergo erythroid, myeloid, or megakaryocytic differentiation upon induction, providing a versatile system to study lineage commitment and cancer biology. These cells express the BCR-ABL1 fusion protein and exhibit high proliferative capacity and blocked differentiation, hallmarks of CML blast crisis. The DNTTIP1 knockout in this context allows exploration of how transcriptional dysregulation influences leukemogenesis and differentiation.
DNTTIP1 (TdIF1) is a transcriptional corepressor that binds and inhibits terminal deoxynucleotidyltransferase (TdT) and recruits histone deacetylase 1 (HDAC1) to chromatin. Through interactions with HDAC1 and the NuRD complex, DNTTIP1 mediates transcriptional silencing of target genes, contributing to DNA repair and chromatin remodeling. It functions upstream of HDAC1-targeted genes, promoting histone deacetylation and gene repression. Disruption of DNTTIP1 removes this repression, allowing investigation of its role in coordinating transcriptional networks relevant to cancer and acute leukemia. Key molecular partners include TdT, HDAC1, and corepressor components.
Knocking out DNTTIP1 in K-562 cells is significant due to the cell line’s differentiation capacity and CML origin. Loss of DNTTIP1 may affect the balance between proliferation and differentiation, impacting leukemic cell survival. This model enables study of how DNTTIP1-mediated repression, involving TdT inhibition and HDAC1 recruitment, influences hematopoietic differentiation pathways. Researchers can assess collective effects on DNA repair efficiency and responses to chemotherapeutics, exploiting the polyclonal knockout population to dissect DNTTIP1-NuRD complex interactions in leukemia.
This DNTTIP1 knockout cell product is well-suited for diverse experimental applications, including dissecting DNA repair mechanisms, investigating transcriptional regulatory networks, and modeling leukemic cell biology. Typical assays include Western blotting to confirm loss of DNTTIP1 protein and quantify TdT levels, RT-qPCR to measure expression changes of HDAC1 target genes, chromatin immunoprecipitation to assess HDAC1 and NuRD complex occupancy, and flow cytometry to monitor differentiation marker expression (e.g., CD235a for erythroid, CD41 for megakaryocytic). DNA repair efficiency can be evaluated using comet assays or ??H2AX foci analysis. The polyclonal knockout format allows robust population-level studies. For technical specifications or ordering information, please contact Ascent Research.
