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Expression analysis of USF1/USF2-depleted B cell response to ionizing radiation

ABSTRACT: Cancer results from the accumulation of critical genetic mutations and the loss of genomic stability. Upon genotoxic insult, cells rapidly activate p53-dependent programs that pause the cell cycle and direct either DNA repair or apoptosis. The long-term transcriptional programs that direct either cell recovery or removal are less well understood. We used RNA interference to investigate the potential of upstream stimulatory factor (USF) 1 and 2 stress-response transcription factors to drive long-term DNA damage responses in the p53-deficient mouse B lymphocyte cell line, M12. Microarray analysis revealed that simultaneously depleting cells of both USF1 and USF2 altered the expression of 755 genes (>1.50-fold change, <0.05 FDR), relative to cells expressing a scrambled shRNA. Ionizing radiation induced widespread and distinct changes in gene expression in control and USF knockdown cells. Seven days after irradiation, 3225 and 2798 genes were differentially expressed in control and USF-depleted cells, respectively, roughly half of which were not shared between the two cell types. Microarray findings were confirmed for a panel of genes responsive to USF knockdown and/or irradiation by RT-qPCR. USF depletion led to the widespread differential expression of genes critical for immune development and function, while impairing the ability to mount a long-term transcriptional response to IR-induced DNA damage. These findings shed further light on transcriptional responses to ionizing radiation that manifest over several days, and provide the first evidence that USF1 and USF2 play overlapping roles in shaping this poorly understood aspect of the DNA damage response.

ORGANISM(S): Mus musculus

PROVIDER: GSE101846 | GEO | 2025/07/21

REPOSITORIES: GEO

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