Glial and muscle embryonal carcinoma cell-specific independent regulation of expression of human JC virus early promoter by cyclic AMP response elements and adjacent nuclear factor 1 binding sites
✍ Scribed by Kumar, Kotlo U.; Tang, Shou-Ching; Pater, Mary M.; Pater, Alan
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 694 KB
- Volume
- 49
- Category
- Article
- ISSN
- 0146-6615
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✦ Synopsis
The human polyoma JC virus (JCV) is a glial cellspecific virus and is the etiological agent for the terminal AIDS-associated brain disease, progressive multifocal leukoencephalopathy IPML). JCV contains several binding sites for transcriptional factors that are important for activity in glial cells, including cyclic AMP (CAMP) response elements (CREs) which are four nucleotides from nuclear factor 1 (NFI) sites within the t w o 98 bp repeat regions. We studied the combined role of cAMP and NFI in regulating the expression of the JCV early promoter-enhancer (JCV,) in differentiating glial and muscle PI9 embryonal carcinoma cells. JCVE expression remained several-fold higher i n the presence of cAMP in glial cells, irrespective of whether the relatively strong activity of JCVE was greatly reduced by NFI site mutations. In contrast, cAMP had no effect in muscle cells, independent of whether the modest activity of JCVE was two-fold higher due to NFI site mutations. The in vivo effects were confirmed with in vitro transcription assays using glial cell extracts, competitors of CRE, and the NFI site, and single repeat JCVE region with mutations in the NFI II/ Ill binding sites as templates. The in vitro results also indicated that the effects were due t o the CREs of JCV, rather than to the indirect effects of CAMP. Overall, the results indicated that NFI and cAMP have independent, different, tissuespecific, and direct effects in the regulation of JCVE. These effects may contribute the neurotropic PML-inducing pattern of expression of JCVE.