HMGN4 Knockout HAP1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population designed for loss-of-function studies of the HMGN4 gene. The product consists of a genetically mixed pool of HAP1 cells carrying targeted disruptions of the HMGN4 coding region introduced by CRISPR/Cas9 nucleases. This polyclonal format minimizes biases from single-cell cloning and is well-suited for pooled functional screens, as well as bulk assays requiring uniform gene inactivation across the sample.
The host cell line, HAP1, is a near-haploid human cell line derived from the KBM-7 chronic myeloid leukemia (CML) line of male origin. Its genome is largely haploid, except for a disomic segment on chromosome 15, which simplifies genetic analysis by reducing gene copy number to one allele. HAP1 cells retain the proliferative capacity and cancer-relevant signaling pathways of their leukemic origin, making them a robust model for leukemia biology and haploid genetic screens.
HMGN4 belongs to the high-mobility group nucleosome-binding protein family and functions as a chromatin architectural factor. It binds directly to the nucleosome core particle, interacting with histone H3 and linker histones, and collaborates with chromatin remodeling complexes to locally decompact chromatin. This activity is regulated by upstream transcription factors and Wnt signaling pathway components; upon signaling, HMGN4 facilitates the transition to an open chromatin state, promoting the recruitment of general transcription factors and RNA polymerase II to target gene promoters. Consequently, HMGN4 regulates the expression of downstream effectors such as cell cycle regulators and apoptotic proteins. Disruption of HMGN4 expression abrogates these regulatory interactions, leading to altered chromatin accessibility and defective transcriptional programs that impact cell proliferation and viability.
In the HAP1 context, the near-haploid genome provides a unique advantage: a single disruptive mutation in HMGN4 produces a complete loss of function without the masking effects of a second allele. This allows researchers to unambiguously attribute phenotypic changes to HMGN4 deficiency. The model is particularly valuable for investigating the role of chromatin structure in leukemogenesis, drug response, and cancer cell survival, offering a platform to identify epigenetic dependencies in malignant cells.
This polyclonal knockout pool supports diverse research applications, including genome-wide CRISPR screens for synthetic lethality or drug resistance modifiers, transcriptomic and epigenomic profiling by RNA-seq and ChIP-qPCR, and functional assays such as proliferation, apoptosis, and drug sensitivity measurements. It is also suitable for protein analysis via western blotting, immunofluorescence, and flow cytometry. This versatile tool enables dissection of chromatin-mediated gene regulation in cancer and aids in target validation for therapeutic development. For further inquiries, please contact Ascent Research.
