Nicotinamide potentiates TSHR and MHC class II promoter activity in FRTL-5 cells.
Here we show that nicotinamide modulates the promoter activity of rat thyrotropin (TSHR) and major histocompatibility complex (MHC) class II genes in rat FRTL-5 thyroid cells, and have identified a novel mechanism for its action. TSHR and MHC class II, are potentiated through reduced expression of a common repressor of these two genes, TSEP-1 (TSHR suppressor element binding protein-1)/YB-1. Thus we show that TSHR mRNA is increased and TSHR promoter activity was concentration-dependently activated from 0 to 40 mM nicotinamide. The promoter lengths of TSHR and MHC class II containing TSEP/YB-1 binding sites were enhanced by 40 mM nicotinamide, but not the ones deleted of these binding sites. TSEP-1/YB-1 binding to the recognition sites in both TSHR and MHC class II promoters was reduced in nicotinamide-treated FRTL-5 nuclear extracts. Nicotinamide reduced the expression of TSEP-1/YB-1 mRNA and TSEP-1/YB-1 protein in the nucleus.
Ohe
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Third Department of Internal Medicine, Kyushu University Faculty of Medicine, Fukuoka, Japan.
Ikuyama
S
S
Takayanagi
R
R
Kohn
L D
LD
Nawata
H
H
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005802:Genes, MHC Class II; D007371:Interferon-gamma / Q000494:pharmacology; D051839:NFI Transcription Factors; D009536:Niacinamide / Q000494:pharmacology*; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins; D012097:Repressor Proteins / Q000378:metabolism; D013961:Thyroid Gland / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013972:Thyrotropin / Q000235:genetics*; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D009536:Niacinamide; D007371:Interferon-gamma; D013972:Thyrotropin