This complex, called interferon-stimulated gene factor 3 (ISGF3), translocates to the nucleus where it binds interferon-stimulated response elements (ISREs
) leading to expression of interferon stimulated genes (ISGs) .
(36) Then ISGF3 was translocated to the nucleus, bound to IFN-stimulated response elements (ISREs
) within the promoters of interferon-stimulated genes (ISGs) and activated the transcription of ISGs.
In this region, IFN-stimulated response elements (ISREs
) and the IFN[gamma]-activation sequence (GAS) have been identified as binding sties for members of the IFN regulatory factor (IRF) family, IFN-stimulated gene factor 3 (ISGF3 composed of Stat1, Stat2, and IRF-9), and Stat1 [25-28, 30], which mediate responsiveness to IFNs.
Type I IFNs induce formation of ISGF3 which complexes with a 48 kDa DNA binding protein and binds to ISREs. Formation of the ISGF3 complex and its migration to the nucleus requires tyrosine phosphorylation of STAT1 and STAT2 proteins by JAK1.
Endometrial proteins induced by IFNT e.g., B2M (p2-microglobulin) in sheep (Vallet et al., 1991) and 12 and 28 kDa ubiquitin-like proteins in cattle (Rueda et al., 1993), may be important markers of gene expression in response to early activated transcription factors that bind to IFN stimulated response elements (ISRE) on target genes (Figure 2).
Esses complexos se ligam a regioes definidas no DNA chamadas de elementos responsivos a estimulacao por interferons (ISREs
) que regulam a expressao de ISGs (HANSEN et al., 1999).
The IDO1 gene has two interferon-stimulated response elements (ISREs) and IFN-[gamma]-activated site (GAS) element sequences in the 5,-flanking region [23-25].
Taylor, "Importance of the two interferon-stimulated response element (ISRE) sequences in the regulation of the human indoleamine 2,3-dioxygenase gene," The Journal of Biological Chemistry, vol.
Overall, HLA class I genes present two main regulatory modules in the proximal promoter region (200 bases upstream to the translation start point), including (i) the Enhancer A (EnhA) combined with an interferon-stimulated response element (ISRE) and (ii) the SXY module, in which the transcription apparatus is mounted (Figure 1) [19-24].
ISRE is a target site for the interferon regulatory factor family, including the interferon regulatory factor-1 (IRF-1, activator), IRF-2, and IRF-8 (inhibitors) .
The nucleotide sequence of ISRE also varies among HLA class I loci.
ISRE is also a target for other protein complexes that may mediate HLA class I transactivation.