The ATXN1 Knockout HT29 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population targeting the ATXN1 gene in the human HT29 colorectal adenocarcinoma line. This loss-of-function model is generated via Cas9 and guide RNAs directed against ATXN1, producing a heterogeneous pool of edited cells. It enables studies of ATXN1-dependent transcriptional repression in colorectal cancer and neurodegenerative disease contexts. This tool is suitable for pooled functional screens and bulk biochemical assays.
The HT29 cell line is derived from a human female colorectal adenocarcinoma and serves as a well-characterized model of intestinal epithelial physiology. HT29 cells display features of enterocytic differentiation upon appropriate stimulation and are extensively employed in studies of colon cancer pathogenesis, cell polarity, and mucosal barrier function. HT29 cells can be induced to differentiate into enterocyte-like cells, making them valuable for differentiation studies.
ATXN1 functions as a transcriptional repressor by forming a complex with Capicua (CIC). This ATXN1-CIC repressor complex binds specific DNA motifs to silence genes involved in neuronal function and development. ATXN1 activity is controlled by upstream Notch signaling through the Notch intracellular domain (NICD) and by phosphorylation by various kinases. The complex interacts with regulatory partners including ATXN1L, PQBP-1, RBM17, and the SMRT corepressor, integrating transcriptional repression with RNA metabolism. Knockout of ATXN1 in HT29 cells abolishes this repression, potentially derepressing target genes and altering downstream expression programs.
In the colorectal adenocarcinoma setting of HT29, ATXN1 knockout is expected to relieve suppression of ATXN1-CIC target genes, which may influence cell proliferation, differentiation, and survival. This model thus provides a platform to dissect how ATXN1-dependent transcriptional control affects oncogenic signaling pathways in the intestinal epithelium, contributing to our understanding of colorectal tumorigenesis and intestinal homeostasis.
This polyclonal knockout cell product supports a wide array of research applications, including the elucidation of ATXN1’s role in colorectal cancer, mechanistic modeling of spinocerebellar ataxia type 1 (SCA1), and high-throughput drug screening for SCA1 therapies. The heterogeneous population is amenable to bulk assays such as Western blotting, RT-qPCR, and co-immunoprecipitation, as well as RNA-seq for transcriptome-wide analysis. Cell proliferation assays (MTT/BrdU) and flow cytometry for cell cycle evaluation allow functional phenotyping in cancer-relevant contexts. The system also enables studies of intestinal epithelial gene regulation and Notch signaling dynamics. For further details, please contact Ascent Research.
