Dataset Information

FOXA2 potently represses NF-κB–dependent transcription from viral promoters in liver cells

ABSTRACT: The transcription factor Forkhead box A2 (FOXA2) is a key regulator of endoderm development and mature endoderm-derived organs, including the liver, and tight control of its expression and activity is paramount for proper execution of developmental and homeostatic gene programs. Despite its established role as a pioneer transcription factor and transcriptional activator, FOXA2 exhibited robust repressive activity in differentiated liver cells. FOXA2 over-expression led to widespread repression of endogenous genes, including autorepression of the FOXA2 locus, and to dramatic suppression of viral regulatory elements. Among these, the SV40 virus early promoter—an essential driver of viral replication and cellular transformation—was strongly repressed by FOXA2. Repression was most pronounced on regulatory elements whose activity is dependent on nuclear factor κB (NF-κB). For the SV40 early promoter, NF-κB binding sites were necessary and sufficient for FOXA2–dependent repression. Consistent with this, the DNA binding domain of FOXA2 was sufficient to mediate repression of NF-κB–driven promoters. EMSA and immunoblot analyses indicated that FOXA2 does not repress these promoters through direct competition with NF-κB for DNA binding. Instead, FOXA2 expression was associated with reduced NF-κB protein abundance, at least in part through proteasome-dependent degradation, revealing a novel indirect mechanism by which FOXA2 constrains NF-κB–dependent transcription. Since many viruses, including SV40 and HIV-1, rely heavily on NF-κB activity to drive early gene expression and the transition from latency to productive infection, our findings suggest that FOXA2 may function as a host-derived, context-dependent restriction factor that limits viral gene expression in differentiated tissues.

ORGANISM(S): Homo sapiens

PROVIDER: GSE319902 | GEO | 2026/07/16

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Aim： Use microarray analysis to understand the molecular mechanism underlying the effect of aristolochic acid (AA), a major active component of plants from the Aristolochiaceae family, in normal human kidney (HK-2) cells. Methods： HK-2 cells were treated with AA for 24 hours and cell viability was measured by a 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay. Complementary DNA microarrays were used to investigate the gene expression pattern of HK-2 cells exposed to AA and the results of this study were in triplicate. Quantitative real-time RT-PCR assay was used to verify the microarray data for selected nuclear factor kappa B (NF-κB)-regulated genes. Furthermore, subcellular localization of NF-κB p65 was visualized by immunofluorescence confocal microscopy in HK-2 cells. NF-κB activity was examined by luciferase reporter assay in HK-2/NF-κB transgenic cells. Results： AA exhibited a dose-dependent cytotoxic effect in HK-2 cells and induced alterations in gene expression profiles related to DNA damage response, stress response, etc. In addition, 9 biological pathways associated with immunomodulatory functions were down-regulated in AA-treated HK-2 cells. Network analysis revealed that NF-κB played a central role in the network topology. Among NF-kB-regulated genes, 8 differentially expressed genes were verified by real-time RT-PCR. The inhibition of NF-κB activity by AA was further confirmed by immunofluorescence confocal microscopy and by NF-κB luciferase reporter assay. Conclusion： Our data revealed that AA could suppress NF-κB activity in normal human cells, perhaps partially accounting for the reported anti-inflammatory effects of some plants from the genus Aristolochia. HK-2 cells were grown in keratinocyte serum-free basal medium (Gibco) supplemented with 5 ng/ml of recombinant epidermal growth factor and 50 μg/ml of bovine pituitary extract without antibiotics in 5 % CO2 at 370C. HK-2 cells were seeded in 25-T flasks and incubated for 24 h before aristolochic acid treatment. Aristolochic acid (10 90 μM) were added to HK-2 cells for 24 h. The control cells received equal amounts of water only.

Dataset Information

FOXA2 potently represses NF-κB–dependent transcription from viral promoters in liver cells

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets