Interferon-beta promoters contain a DNA element that acts as a position-independent silencer on the NF-kappa B site.

AUTOR(ES)

Nourbakhsh, M

RESUMO

The human interferon-beta (IFN-beta) promoter contains several functional domains that contribute to its virus-inducible regulation. One of them, PRDII, and NF-kappa B-binding sequence, can function as a constitutively activating element. Due to the presence of a negative regulatory domain that mediates a constitutive repression the natural IFN-beta promoter is silent in the non-induced state. Within this domain we have delimited an 11 bp element that acts as a negative regulatory element (NRE) of PRDII. Although the NRE is physically overlapping with PRDII in the IFN-beta promoter, it acts as a position-independent silencer of PRDII. Virus infection, which leads to the transcriptional activation of the IFN-beta promoter, does not alter the negative activity of the NRE on an isolated PRDII. It is the cooperative effect of PRDI and PRDII that is able to overcome the NRE function after virus infection. By UV cross-linking analysis using uninduced and virus-induced nuclear extracts, we show that two factors with molecular masses of approximately 95 and 100 kDa bind to the NRE.

Documentos Relacionados

• Oligonucleotide that binds nuclear factor NF-kappa B acts as a lymphoid-specific and inducible enhancer element.
• Interaction of the v-rel protein with an NF-kappa B DNA binding site.
• Transcriptional inhibition of the interleukin-8 gene by interferon is mediated by the NF-kappa B site.
• NF-kappa B-independent activation of beta-interferon expression in mouse F9 embryonal carcinoma cells.
• Human cytomegalovirus upregulates NF-kappa B activity by transactivating the NF-kappa B p105/p50 and p65 promoters.