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|Title:||Locus-specific transcriptional control of HLA genes|
|Authors:||Soong, T.W. |
|Source:||Soong, T.W.,Hui, K.M. (1992-09-15). Locus-specific transcriptional control of HLA genes. Journal of Immunology 149 (6) : 2008-2020. ScholarBank@NUS Repository.|
|Abstract:||One remarkable genetic feature of the class I MHC genes is their unparalleled degree of genetic polymorphism and diversity. The polymorphism is reflected by the fact that multiple loci encode class I molecules, and for each locus there are multiple alleles. In the course of investigating the regulation of HLA-A and HLA-B mRNA in human colorectal carcinoma cell lines, we have noticed a noncoordinate expression of the HLA mRNA in some of these cell lines. This observation prompted us to make use of these cell lines to study the locus-specific transcriptional regulation of HLA genes. Bandshift and footprint assays revealed at least three distinct and independent DNA-binding factors that bind to the core regulatory element of the HLA-A and HLB-B gene locus. A "novel" DNA-binding factor recognizing the CCAAT motif seems to be important for locus-specific expression of HLA-A mRNA, whereas a different factor which binds to a Sp1-like sequence is crucial for normal HLA-B mRNA expression. In certain colorectal cancer cell lines, underrepresentation of these locus-specific DNA-binding proteins correlates with the locus-specific down-regulation of HLA mRNA. This observation is further supported by experiments which demonstrated that the locus-specific suppression of exogenously introduced TK-chloramphenicol acetyltransferase DNA constructs, containing the "putative" HLA locus-specific DNA core regulatory sequence, is regulated in a locus-specific manner when introduced into these HLA-A- and HLA-B-deficient human colorectal cell lines.|
|Source Title:||Journal of Immunology|
|Appears in Collections:||Staff Publications|
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