{'fraction_non_alphanumeric': 0.033816425120772944, 'fraction_numerical': 0.004830917874396135, 'mean_word_length': 5.170212765957447, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Retinoic Acid-induced Transcriptional Modulation of the Human Interferon-γ Promoter*

Disregulation of vitamin A metabolism is able to generate different immunological effects, including altered response to infection, reduced IgG production, and differential regulation of cytokine gene expression (including interleukin-2 and −4 and interferon-γ (IFN-γ)). In particular, IFN-γ gene expression is significantly affected by vitamin A and/or its derivatives (e.g. retinoic acid (RA)). Here, we analyze the effect of retinoic acid on IFN-γ transcription. Transient transfection assays in the human T lymphoblastoid cell line Jurkat demonstrated that the activation of the IFN-γ promoter was significantly down-regulated in the presence of RA. Surprisingly, two different AP-1/CREB-ATF-binding elements situated in the initial 108 base pairs of the IFN-γ promoter and previously shown to be critical for transcriptional activity were unaffected by RA. Utilizing promoter deletions and electrophoretic mobility shift analysis, we identified a USF/EGR-1-binding element cooperating in the modulation of IFN-γ promoter activity by RA. This element was found to be situated in a position of the IFN-γ promoter close to a silencer element previously identified in our laboratory. These results suggest that direct modulation of IFN-γ promoter activity is one of the possible mechanisms involved in the inhibitory effect of retinoids on IFN-γ gene expression.