title: Epigenetic Silencing of the Human 18 kDa Translocator Protein in a T Cell Leukemia Cell Line.
abstract: The mitochondrial membrane 18 kDa translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is constitutively expressed in most organs, most abundantly in hormonal tissue and cells of mononuclear phagocyte lineage, while in the brain, TSPO expression is induced in the wake of injury, inflammation, and neurodegeneration. Increased TSPO expression is also prominent in several cancerous tissues where it appears to correlate with the degree of malignancy. Currently, TSPO is thus actively investigated as a generic biomarker for disease activity and a therapeutic target for a wide range of diseases. In this study, we report a Jurkat human T cell leukemia cell line that has only trace expression of TSPO mRNA. Through the use of bisulphite genomic sequencing, we show that the Jurkat TSPO promoter is highly methylated except for CpG sites that are adjacent to the transcription start site. Control measurements in HEK-293, HeLa, and U87-MG cells with high TSPO mRNA expression showed low levels of TSPO promoter methylation. Demethylation with 5-aza-2'-deoxycytidine (5-aza-dC) caused a dose-dependent increase in TSPO mRNA with a corresponding demethylation of the TSPO promoter in Jurkat cells. Treating HeLa and U87-MG cells with 5-aza-dC caused no change in the level of TSPO mRNA. These observations confirm the epigenetic regulation of TSPO and suggest it to be a more common mechanism by which the differential expression of TSPO in various cell types and in health and disease may be explained.
authors.affiliation: 1 Australian Nuclear Science and Technology Organization , Lucas Heights, Australia .
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Middleton
authors.affiliation: 1 Australian Nuclear Science and Technology Organization , Lucas Heights, Australia .|2 Department of Health Technology and Informatics, Hong Kong Polytechnic University , Hung Hom, Hong Kong, China .
authors.forename: Winnie Wai-Ying
authors.initials: WW
authors.lastname: Kam
authors.affiliation: 1 Australian Nuclear Science and Technology Organization , Lucas Heights, Australia .|3 National Imaging Facility, Brain and Mind Centre and Faculty of Health Sciences, University of Sydney , Camperdown, Australia .
authors.forename: Guo-Jun
authors.initials: GJ
authors.lastname: Liu
authors.affiliation: 1 Australian Nuclear Science and Technology Organization , Lucas Heights, Australia .|3 National Imaging Facility, Brain and Mind Centre and Faculty of Health Sciences, University of Sydney , Camperdown, Australia .
authors.forename: Richard B
authors.initials: RB
authors.lastname: Banati
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001483:Base Sequence; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics; D000077209:Decitabine; D044127:Epigenesis, Genetic / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D015458:Leukemia, T-Cell / Q000473:pathology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D018079:Receptors, GABA / Q000172:deficiency* / Q000235:genetics*
chemical_list: D018079:Receptors, GABA; C499229:TSPO protein, human; D000077209:Decitabine; D001374:Azacitidine
keywords: Jurkat; TSPO; methylation