HDAC1 Knockout HCT 116 Polyclonal Cells represent a pooled population of HCT 116 colorectal carcinoma cells genetically modified using CRISPR/Cas9 to disrupt the HDAC1 gene. This polyclonal knockout product provides a functional loss-of-function model for studying histone deacetylase 1 without clonal isolation, preserving heterogeneity inherent to the edited cell population.
The HCT 116 cell line is a widely utilized epithelial colorectal adenocarcinoma model derived from a male patient, characterized by microsatellite instability (MSI-H) and activating mutations in KRAS (G13D) and PIK3CA. These cells exhibit constitutive WNT pathway activation, with high beta-catenin and COX-2 expression, making them suitable for cancer biology and drug screening applications.
HDAC1 is a class I histone deacetylase that removes acetyl groups from lysine residues on histone tails, particularly H3K9ac and H3K14ac, leading to chromatin compaction and transcriptional repression. It is regulated by upstream factors such as E2F1, MYC, p53, and RB1, and its activity is modulated by phosphorylation via CK2 and SUMOylation. HDAC1 interacts with corepressor complexes including SIN3A, NuRD (via MTA2), and CoREST, and deacetylates both histones and non-histone proteins, including p53, STAT3, and NF-??B p65. Through these interactions, HDAC1 represses key genes such as CDKN1A (p21) and BCL2, thereby promoting cell cycle progression and inhibiting apoptosis. It functions within multiple signaling cascades, including p53, TGF-??, Wnt, Notch, JAK-STAT, NF-??B, and MAPK pathways, and its overexpression is associated with oncogenic transformation by silencing tumor suppressors.
In colorectal cancer, HDAC1 is frequently overexpressed, contributing to aberrant gene silencing. Disruption of HDAC1 in HCT 116 cells leads to hyperacetylation of histone H3, derepression of target genes such as CDKN1A and BAX, resulting in cell cycle arrest and activation of apoptosis. The interplay with mutant KRAS and active WNT signaling provides a relevant context for investigating epigenetic mechanisms underlying colorectal tumorigenesis and for evaluating the therapeutic potential of HDAC inhibitors such as vorinostat and trichostatin A.
This HDAC1 knockout polyclonal cell pool is suited for diverse research applications, including epigenetic regulation studies, cancer functional genomics, and drug target validation. It can be employed in assays such as western blotting for HDAC1 and global histone acetylation levels, RT-qPCR for CDKN1A and BAX expression, ChIP-qPCR for promoter histone acetylation, immunofluorescence localization, flow cytometric analysis of apoptosis (Annexin V) and cell cycle (PI staining), colony formation assays, and drug sensitivity testing with HDAC inhibitors. Migration and invasion assays, as well as RNA-seq for transcriptome profiling, further support mechanistic and discovery studies. For additional information and technical support, please contact Ascent Research.
