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A HLA class I cis ‐regulatory element whose activity can be modulated by hormones
Author(s) -
Sim Bee C.,
Hui Kam M.
Publication year - 1994
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910590512
Subject(s) - biology , enhancer , human leukocyte antigen , gene , hormone response element , response element , regulatory sequence , context (archaeology) , regulation of gene expression , mhc class i , genetics , promoter , major histocompatibility complex , gene expression , estrogen receptor , antigen , cancer , paleontology , breast cancer
To elucidate the basis of the down‐regulation in major histocompatibility complex (MHC) class I gene expression and to identify possible DNA‐binding regulatory elements that have the potential to interact with class I MHC genes, we have studied the transcriptional regulation of class I HLA genes in human breast carcinoma cells. A 9 base pair (bp) negative cis ‐regulatory element (NRE) has been identified using band‐shift assays employing DNA sequences derived from the 5′‐flanking region of HLA class I genes. This 9‐bp element, GTCATGGCG, located within exon I of the HLA class I gene, can potently inhibit the expressior of a heterologous thymidine kinase (TK) gene promoter and the HLA enhancer element. Furthermore, this regulatory element can exert its suppressive function in either the sense or anti‐sense orientation. More interstingly, NRE can suppress dexamethasone‐mediated gene activation in the context of the reported glucocorticoidresponsive element (GRE) in MCF‐7 cells but has no influence on the estrogen‐mediated transcriptional activation of MCF‐7 cells in the context of the reported estrogen‐responsice element (ERE). Furthermore, the presence of such a regulatory element within the HLA class I gene whose activity can be modulated by hormones correlates well with our observation that the level of HLA class I gene expression can be down‐regulated by hormones in human breast carcinoma cells. Such interactions between negative regulatory elements and specific hormone trans‐activators are novel and suggest a versatile form of transcriptional control.