Site alpha is crucial for two routes of IFN gamma-induced MHC class I transactivation: the ISRE-mediated route and a novel pathway involving CIITA.
The constitutive and cytokine-induced levels of major histocompatibility (MHC) class I expression are tightly controlled at the transcriptional level. In this study, it is shown that the cis-acting regulatory element site alpha of the MHC class I promoter is essential for the IFN gamma-induced transactivation of MHC class I gene expression through the ISRE. Moreover, it was discovered that the class II transactivator (CIITA), which is itself under the control of the IFN gamma induction pathway, strongly transactivates MHC class I gene expression and exerts its activity through site alpha. Therefore, site alpha is a crucial regulatory element, mediating the classic route of IFN gamma induction via the ISRE as well as a novel route of MHC class I transactivation involving CIITA.
Gobin
S J
SJ
Department of Immunohaematology and Blood Bank, University Hospital Leiden, The Netherlands.
Peijnenburg
A
A
Keijsers
V
V
van den Elsen
P J
PJ
D051697:Activating Transcription Factor 1; D001665:Binding Sites / Q000235:genetics; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation / Q000276:immunology; D005805:Genes, MHC Class I / Q000276:immunology*; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D009154:Mutation; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic / Q000276:immunology*; D013724:Teratoma; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics / Q000276:immunology*
D051697:Activating Transcription Factor 1; D004268:DNA-Binding Proteins; D015395:Histocompatibility Antigens Class I; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D007371:Interferon-gamma