title: Interferons increase transcription of a major histocompatibility class I gene via a 5' interferon consensus sequence.
abstract: Interferons (IFNs) augment expression of major histocompatibility class I genes in many cells. To study the effect of IFNs on transcription of class I genes, we prepared and tested activity of chloramphenicol acetyltransferase (CAT) hybrid genes in which the cat gene is under the control of the 5' flanking region of the murine H-2Ld gene. NIH 3T3 cells transiently transfected with a cat construct having the sequence from position -210 to -134 showed a four- to fivefold increase in CAT activity when treated with IFN-alpha/beta. This sequence contains the IFN consensus sequence (ICS) shared among IFN-inducible genes, as well as the class I regulatory element (CRE) that controls up and down regulation of class I gene expression. To determine the precise sequence requirement for the IFN action, the ICS and CRE were independently placed upstream of the class I or a heterologous simian virus 40 promoter, and CAT activity was tested. The ICS, but not the CRE, enhanced activity of both promoters by about twofold upon exposure to IFN-alpha/beta, although greater responses were noted when the ICS and CRE were combined. These results demonstrate that the ICS alone is capable of enhancing promoter activity in response to IFN-alpha/beta treatment and that the CRE exerts a synergistic effect. Further, we show that the ICS functions as an inducible enhancer since it acts regardless of its orientation and distance in the simian virus 40 promoter.
mesh_terms: D000123:Acetyltransferases / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D015500:Chloramphenicol O-Acetyltransferase; D004247:DNA / Q000235:genetics; D004742:Enhancer Elements, Genetic / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006183:H-2 Antigens / Q000235:genetics; D007370:Interferon Type I / Q000494:pharmacology*; D008285:Major Histocompatibility Complex / Q000187:drug effects*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D006183:H-2 Antigens; D007370:Interferon Type I; D004247:DNA; D000123:Acetyltransferases; D015500:Chloramphenicol O-Acetyltransferase