A novel element and a TEF-2-like element activate the major histocompatibility complex class II transactivator in B-lymphocytes.
Major histocompatibility complex (MHC) class II molecules play a central role in immune responses, and transcription of this family of genes requires the MHC class II transactivator (CIITA). CIITA has four promoters, which are transcribed in a tissue-specific manner. CIITA promoter III is constitutively active in mature B-lymphocytes. This report now describes the minimal 319-base pair promoter region necessary for maximal transcriptional activity in B-lymphocytes. Ultraviolet light and dimethylsulfate in vivo genomic footprinting analyses reveal five occupied DNA sequence elements present in intact B-lymphocytes. Functional analysis of these elements using promoter deletions and site-specific mutations demonstrates that at least two of the sites occupied in vivo are critical for transcriptional activity. In vitro protein/DNA analysis suggests that one of the sites is a TEF-2-like element and the other is occupied by a novel transcription activator. In addition, nuclear factor-1 associates with the promoter both in vivo and in vitro. In myeloma cell lines, loss of CIITA transcription correlates with a completely unoccupied CIITA promoter III. These findings suggest that CIITA transcription in B-lymphocytes is activated through at least two strong promoter elements, while loss of expression in myeloma cells is mediated through changes in promoter assembly.
Ghosh
N
N
H. Lee Moffitt Cancer Center, Department of Biochemistry, University of South Florida, Tampa, Florida 33612, USA.
Piskurich
J F
JF
Wright
G
G
Hassani
K
K
Ting
J P
JP
Wright
K L
KL
D001402:B-Lymphocytes / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D018983:DNA Footprinting; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005802:Genes, MHC Class II; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; C501170:GT-IC protein, human; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators