The ATXN1L Knockout HAP1 Polyclonal Cells product offers a CRISPR/Cas9-edited polyclonal cell population in which the ATXN1L gene has been disrupted. This loss-of-function model provides a heterogeneous pool of knockout cells without clonal selection, enabling robust functional studies of ATXN1L-dependent transcriptional regulatory networks.
HAP1 is a near-haploid human cell line derived from the KBM-7 chronic myeloid leukemia (CML) line (blast crisis stage). The adherent HAP1 variant is p53-deficient and maintains a largely haploid karyotype, which minimizes genetic redundancy and simplifies CRISPR-based gene targeting. These features make HAP1 a widely used model for genetic screening, drug response profiling, and mechanistic studies in cancer biology.
ATXN1L encodes a transcriptional corepressor that forms a complex with the DNA-binding protein CIC. This complex is recruited to promoters of target genes such as the ETS transcription factors ETV1, ETV4, and ETV5, mediating transcriptional repression. The MAPK/ERK signaling pathway relieves this repression: upon activation, MAPK phosphorylates CIC, targeting it for degradation and releasing the inhibition of ETS target genes. ATXN1L also interacts with its paralog ATXN1 and RNA-binding proteins, contributing to context-dependent regulatory functions in notochord development and circadian rhythms. Consequently, ATXN1L knockout alters the expression of CIC-controlled effectors and impacts diverse cellular processes.
In the p53-deficient, near-haploid HAP1 background, ATXN1L disruption eliminates a critical node connecting MAPK/ERK signaling to ETS transcription factor output. This simplified genetic setting is particularly advantageous for studying how oncogenic kinase signals override CIC-dependent repression, an event implicated in tumorigenesis. The model allows clear dissection of the interplay between the ATXN1L?CCIC complex and upstream MAPK activity without the confounding effects of chromosomal amplifications or wild-type p53 responses.
Typical applications of the ATXN1L Knockout HAP1 Polyclonal Cells include RNA-seq or ChIP-seq experiments to map ATXN1L- and CIC-regulated transcriptomes and genomic binding sites, RT-qPCR and Western blotting to validate expression changes in ETV1/4/5 and CIC protein levels, and reporter gene assays to measure ETS-responsive promoter activity. The model also supports drug discovery efforts, such as evaluating MAPK pathway inhibitors for their ability to restore transcriptional repression, and functional assays like proliferation or migration tests. For spinocerebellar ataxia type 1 (SCA1) research, this knockout line enables comparative studies with ATXN1. For further information or to discuss custom applications, please contact Ascent Research.
