The KDM6A Knockout Jurkat Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout population engineered for loss-of-function studies of KDM6A in a human T lymphocyte background. This heterogeneous pool of Jurkat cells with targeted gene disruption enables the study of KDM6A-dependent epigenomic and transcriptional regulation in the context of T-cell leukemia.
The Jurkat cell line, derived from a 14-year-old male with acute T cell leukemia, is a widely used model for T cell signaling, activation, and apoptosis. These suspension cells retain key T lymphocyte surface markers and active Notch and T cell receptor pathways, making them ideal for mechanistic studies of T-cell development and leukemogenesis.
KDM6A encodes a histone demethylase that specifically removes the repressive H3K27me3 mark, thereby facilitating transcriptional activation. It functions within complexes containing KMT2D (MLL4), ASXL2, RBBP5, WDR5, and PAXIP1, and is regulated by upstream signals including TGF-beta, the Notch intracellular domain (NICD), retinoic acid, HOX proteins, and SMAD2/3. KDM6A promotes expression of downstream targets such as HOXA cluster genes, CDKN1A (p21), BMP2, WNT4, NANOG, and SOX2. In the Notch pathway, the NICD?CRBPJ?CMAML1 complex recruits KDM6A to erase H3K27me3 at Notch-responsive elements, driving transcription of genes essential for T cell lineage commitment and leukemic proliferation.
Jurkat cells lacking functional KDM6A exhibit increased global H3K27me3, leading to silencing of genes normally activated during T cell development and Notch-driven growth. This epigenetic shift can dysregulate HOXA gene expression and other differentiation programs, potentially altering leukemic phenotypes. The model recapitulates features of T-cell acute lymphoblastic leukemia, where KDM6A mutations frequently co-occur with NOTCH1 and KMT2D alterations, and is also relevant to acute myeloid leukemia and bladder cancer, where KDM6A acts as a tumor suppressor.
These polyclonal knockout cells are suited for ChIP-seq and Western blotting to map H3K27me3 changes, RNA-seq and RT-qPCR to define KDM6A-dependent transcription, and ATAC-seq to assess chromatin accessibility. Functional studies include flow cytometric analysis of T cell markers, Notch reporter luciferase assays, and proliferation and apoptosis tests. The product enables histone modifier drug screening and dissection of crosstalk between TGF-beta, retinoic acid, and Notch signaling. For further information or custom inquiries, please contact Ascent Research.
