title: Modulation of HLA-G expression.
abstract: Recent studies demonstrated that HLA-G transcription is in some cells silenced by epigenetic mechanisms as DNA methylation and histone modification. Accordingly HLA-G gene transcriptions can be activated in such cells by demethylating agent or by inhibitors of histone deacetylation. In addition to epigenetic alterations HLA-G gene transcription can be activated by stress. In the present study these aspects of HLA-G expression are re-examined and a new inhibitor of histone deacetylation (valproic acid) and hypoxia mimetic chemical (CoCl2) are included. The highest activation of HLA-G transcription was achieved by treatment of choriocarcinoma JAR and lymphoblastoid RAJI cell lines with demethylating agent 5-aza-2 - deoxycytidine. Treatment of JAR and RAJI cells with histone deacetylase inhibitors (sodium butyrate and valproic acid) also enhanced HLA-G transcription. Nevertheless this increase in HLA-G expression was low as compared with activation by 5-aza-2 - deoxycytidine. The hypoxia mimetic agents (desferrioxamine or CoCl2) had no detectable effect on HLA-G gene transcription in examined cells. Relatively high increase of HLA-G transcription was detected in JAR and RAJI cells exposed to heat shock treatment. Interestingly heat shock induced high expression of HLA-G6 transcript in JAR cells. Heat shock treatment had no effect on alternative splicing of constitutively expressed HLA-G mRNA in choriocarcinoma cell line JEG-3. HLA-G1 protein expression was induced in JAR and RAJI cell lines by 5-aza-2 - deoxycytidine. In agreement with the differences in the levels of HLA-G transcripts JAR cells express more of HLA-G1 protein than RAJI cells.
authors.affiliation: Cancer Research Institute, Slovak Academy of Sciences, 833 91 Bratislava, Slovak Republic. exonpola@savba.sk
authors.forename: K
authors.initials: K
authors.lastname: Polakova
authors.forename: E
authors.initials: E
authors.lastname: Bandzuchova
authors.forename: J
authors.initials: J
authors.lastname: Tirpakova
authors.forename: D
authors.initials: D
authors.lastname: Kuba
authors.forename: G
authors.initials: G
authors.lastname: Russ
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001483:Base Sequence; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D000077209:Decitabine; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044127:Epigenesis, Genetic / Q000187:drug effects; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006680:HLA Antigens / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics*; D006358:Hot Temperature; D006801:Humans; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger; D014635:Valproic Acid; D000077209:Decitabine; D001374:Azacitidine