Expression of major histocompatibility complex (MHC) class I genes in astrocytes correlates with the presence of nuclear factors that bind to constitutive and inducible enhancers.
The molecular basis of constitutive and inducible major histocompatibility complex (MHC) class I gene expression was studied in murine astrocytes in primary culture. Astrocytes constitutively expressed MHC class I molecules and treatment of these cells with interferon-gamma (IFN-gamma) further induced expression. The conserved region containing the upstream MHC class I regulatory element (MHC-CRE) and juxtaposed interferon consensus sequence (ICS) enhanced constitutive MHC class I promoter activity. As seen with cell surface expression of MHC molecules, treatment of astrocytes with IFN-gamma increased MHC class I promoter activity. Inducible expression required the presence of the MHC-CRE/ICS enhancer region. Nuclear factors that bind to the MHC-CRE and ICS were constitutively expressed in cultured astrocytes and IFN-gamma treatment further induced binding activity both to the MHC-CRE and ICS and correlated with induction of MHC class I gene expression. This study identifies the MHC-CRE and ICS as the major cis elements in controlling MHC class I promoter activity and suggests that the expression of nuclear factor binding activities to these enhancer elements is a basic transactivating mechanism for the expression of MHC class I genes in astrocytes.
Massa
P T
PT
Department of Neurology, State University of New York, Syracuse 13210.
Hirschfeld
S
S
Levi
B Z
BZ
Quigley
L A
LA
Ozato
K
K
McFarlin
D E
DE
D000818:Animals; D001253:Astrocytes / Q000276:immunology*; D001483:Base Sequence; D015152:Blotting, Northern; D046508:Culture Techniques; D004268:DNA-Binding Proteins / Q000502:physiology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D011401:Promoter Regions, Genetic / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology; D014162:Transfection
D004268:DNA-Binding Proteins; D015395:Histocompatibility Antigens Class I; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D007371:Interferon-gamma