The HDAC4 Knockout AGS Polyclonal Cells are a human gastric adenocarcinoma cell population engineered by CRISPR/Cas9-mediated disruption of the HDAC4 gene. This polyclonal knockout product contains a heterogeneous pool of AGS cells carrying loss-of-function mutations introduced by Cas9, offering a robust loss-of-function model without clonal selection. The cells are provided as a ready-to-use format for direct application in cancer biology and epigenetic research.
The parental AGS cell line was derived from a gastric adenocarcinoma of a 54-year-old Caucasian female and is widely employed as a model for gastric cancer. These epithelial cells maintain hallmark features of the disease, including aberrant activation of oncogenic pathways, and provide a physiologically relevant context for studying tumor suppressors and epigenetic regulators.
HDAC4 is a class IIa histone deacetylase that represses transcription by deacetylating histones H3 and H4 and non-histone substrates including p53 and HIF-1??. Phosphorylation by CaMKII and CaMKIV promotes 14-3-3 binding and nuclear export of HDAC4, while dephosphorylation by PP2A restores nuclear localization. Nuclear HDAC4 interacts with MEF2 transcription factors (MEF2A, MEF2C, MEF2D) and corepressors HDAC3/NCoR-SMRT to silence genes such as p21, cyclin D1, and Bcl-2. HDAC4 activity is further modulated by upstream signals from p53, ??-catenin/TCF, and PKD, integrating pathways like MAPK/ERK and CaMK.
Within AGS gastric cancer cells, HDAC4 contributes to cellular transformation by repressing transcription of tumor suppressors and pro-apoptotic factors. CRISPR-mediated knockout relieves this repression, leading to increased histone acetylation at gene promoters such as p21 and cyclin D1, resulting in cell cycle arrest and apoptosis. This polyclonal knockout system enables detailed dissection of HDAC4??s role in epigenetic silencing and its cross-talk with p53 and MEF2 pathways, while preserving the heterogeneity of the tumor cell population.
This product is suitable for a wide range of applications, including gastric cancer biology, epigenetic regulation, and preclinical testing of HDAC inhibitors. Researchers can utilize western blotting to assess HDAC4 depletion and global acetyl-H3/H4 levels, RT-qPCR to quantify p21 and cyclin D1 expression, and MTT or Annexin V assays to monitor proliferation and apoptosis. Additional assays such as transwell migration, ChIP-qPCR for histone acetylation at target promoters, and immunofluorescence for HDAC4 localization provide mechanistic insight. Co-immunoprecipitation enables detection of MEF2 interactions, while phospho-specific antibodies permit analysis of upstream kinase regulation. The cells also serve as a platform for drug sensitivity screens. For technical inquiries and ordering, please contact Ascent Research.
