HDAC4 Knockout 143B Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the 143B human osteosarcoma line, generated to disrupt expression of the HDAC4 gene. This pooled loss-of-function model avoids clonal selection, preserving genetic heterogeneity while abolishing HDAC4 function, and is suited for phenotypic screening of histone deacetylase-dependent processes.
The parental 143B cell line originates from a primary human osteosarcoma and exhibits high tumorigenicity and metastatic capacity. Widely adopted in bone cancer research, this model is used to study tumor initiation, growth, and dissemination, and to evaluate therapeutic strategies targeting epigenetic regulators.
HDAC4 is a class IIa histone deacetylase that functions as a transcriptional corepressor by deacetylating lysine residues on histones H3 and H4 and non-histone substrates. Its activity and localization are controlled by phosphorylation-dependent binding to 14-3-3 chaperones. In the nucleus, HDAC4 interacts with MEF2A and MEF2C and recruits corepressor complexes containing NCOR1 and HDAC3. Upstream kinases including CaMKII, CaMKIV, PKD1, and AMPK regulate its shuttling, while it transduces signals from pathways such as CaMK, PKD, Wnt/??-catenin, and TGF-??. Key downstream targets include MEF2 transcription factors, Runx2, NF-??B, p53, and HIF-1??, implicating HDAC4 in cell proliferation, differentiation, and apoptosis.
In osteosarcoma, HDAC4 is associated with tumor malignancy, metastasis, and drug resistance. Its knockout in 143B provides a direct platform to interrogate epigenetic mechanisms driving bone cancer. Loss of HDAC4 function allows systematic analysis of acetylome alterations, MEF2-dependent transcriptional changes, and shifts in cellular sensitivity to chemotherapeutics, thereby facilitating identification of targetable vulnerabilities.
Representative uses include western blotting for acetyl-histone levels, RT-qPCR of HDAC4 target genes, cell proliferation, migration, and colony formation assays. The polyclonal population is also amenable to immunofluorescence visualization of MEF2 localization, co-immunoprecipitation of HDAC4 complexes, and flow cytometric assessment of apoptosis and cell cycle. For further information, please contact Ascent Research.
