X-Box-Binding Proteins Positively and Negatively Regulate Transcription of the HLA-DRA Gene Through Interaction with Discrete Upstream W and V Elements

Previous reports have identified that the class II box, consisting of the positive regulatory X and Y boxes, is important for expression of all class II major histocompatibility genes. In this paper, we identify additional sequences upstream from the class II box that regulate constitutive transcrip...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1990-10, Vol.87 (19), p.7703-7707
Main Authors: Cogswell, John P., Basta, Patricia V., Jenny P.-Y. Ting
Format: Article
Language:English
Subjects:
Base Sequence
Biological and medical sciences
Cell lines
DNA-Binding Proteins - metabolism
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation
Genes
Genes, MHC Class II
HLA-DR Antigens - genetics
Humans
Molecular and cellular biology
Molecular genetics
Molecular Sequence Data
Nuclear proteins
Oligonucleotides
Plasmids
Promoter regions
Promoter Regions, Genetic
Pyrimidines
RNA
Sequence Homology, Nucleic Acid
Single-Strand Specific DNA and RNA Endonucleases
T lymphocytes
Transcription, Genetic
Transcriptional regulatory elements
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Summary:Previous reports have identified that the class II box, consisting of the positive regulatory X and Y boxes, is important for expression of all class II major histocompatibility genes. In this paper, we identify additional sequences upstream from the class II box that regulate constitutive transcription of a human class II gene, HLA-DRA, in the B-lymphoblastoid cell line Raji. Using 5' promoter deletions, substitution mutants, and nuclease S1 protection assays, we mapped a positive element, called W, between -135 and -117 base pairs and a negative element, called V, from -193 to -179 base pairs. Sequence comparisons revealed that W and V share homology with the HLA-DRA X box situated downstream. Gel-mobility-shift assays confirmed that the Raji nuclear proteins that bound to W and V elements were competed with by an HLA-DRA X-box oligonucleotide. These results suggest that X-box-binding proteins mediate both positive and negative effects on transcription by means of interaction with multiple elements (W, V, and X) within the same HLA-DRA gene.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.87.19.7703