Expression of the MHC class II transactivator (CIITA) type IV promoter in B lymphocytes and regulation by IFN-γ

The MHC class II transactivator (CIITA), the master regulator of MHC class II (MHC II) expression, is a co-activator that controls MHC II transcription. Human B lymphocytes express MHC II constitutively due to persistent activity of CIITA promoter III (pIII), one of the four potential promoters (pI–...

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Published in:	Molecular immunology Vol. 43; no. 6; pp. 519 - 528
Main Authors:	Piskurich, Janet F., Gilbert, Carolyn A., Ashley, Brittany D., Zhao, Mojun, Chen, Han, Wu, Jian, Bolick, Sophia C., Wright, Kenneth L.
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 01-02-2006
Subjects:	B lymphocytes B-Lymphocytes - metabolism Binding Sites CIITA DNA-Binding Proteins Gene Expression Regulation - drug effects Gene Expression Regulation - immunology Histocompatibility Antigens Class II - genetics Humans IFN-γ Interferon Regulatory Factor-1 - metabolism Interferon Regulatory Factor-2 - metabolism Interferon-gamma - pharmacology IRF-1 IRF-2 Nuclear Proteins - genetics Promoter Regions, Genetic - genetics Protein Binding RNA, Messenger - analysis Trans-Activators - genetics IRF-2 CIITA IFN-γ IRF-1 B lymphocytes
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Summary:	The MHC class II transactivator (CIITA), the master regulator of MHC class II (MHC II) expression, is a co-activator that controls MHC II transcription. Human B lymphocytes express MHC II constitutively due to persistent activity of CIITA promoter III (pIII), one of the four potential promoters (pI–pIV) of this gene. Although increases in MHC II expression in B cells in response to cytokines have been observed and induction of MHC II and CIITA by IFN-γ has been studied in a number of different cell types, the specific effects of IFN-γ on CIITA expression in B cells have not been studied. To investigate the regulation of CIITA expression by IFN-γ in B cells, RT-PCR, in vivo and in vitro protein/DNA binding studies, and functional promoter analyses were performed. Both MHC II and CIITA type IV-specific RNAs increased in human B lymphocytes in response to IFN-γ treatment. CIITA promoter analysis confirmed that pIV is IFN-γ inducible in B cells and that the GAS and IRF-E sites are necessary for full induction. DNA binding of IRF-1 and IRF-2, members of the IFN regulatory factor family, was up-regulated in B cells in response to IFN-γ and increased the activity of CIITA pIV. In vivo genomic footprint analysis demonstrated proteins binding at the GAS, IRF-E and E box sites of CIITA pIV. Although CIITA pIII is considered to be the hematopoietic-specific promoter of CIITA, these findings demonstrate that pIV is active in B lymphocytes and potentially contributes to the expression of CIITA and MHC II in these cells.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0161-5890 1872-9142
DOI:	10.1016/j.molimm.2005.05.005