title: Promoter methylation regulates SAMHD1 gene expression in human CD4+ T cells.
abstract: The retrovirus restriction factor SAMHD1 is the first identified mammalian dNTP triphosphohydrolase that is highly expressed in human myeloid lineage cells and CD4(+) T lymphocytes. Although SAMHD1 expression is variable in human cell lines and tissue types, mechanisms underlying SAMHD1 gene regulation have not been defined. Recent studies showed that SAMHD1 is highly expressed in human primary CD4(+) T lymphocytes, but not in some CD4(+) T cell lines. Here, we report that SAMHD1 expression varies among four CD4(+) T cell lines and is transcriptionally regulated. Cloning and sequence analysis of the human SAMHD1 promoter revealed a CpG island that is methylated in CD4(+) T cell lines (such as Jurkat and Sup-T1), resulting in transcriptional repression of SAMHD1. We also found that the SAMHD1 promoter is unmethylated in primary CD4(+) T lymphocytes, which express high levels of SAMHD1, indicating a direct correlation between the methylation of the SAMHD1 promoter and transcriptional repression. SAMHD1 expression was induced in CD4(+) T cell lines by blocking DNA methyltransferase activity, suggesting that promoter methylation is one of the key epigenetic mechanisms by which SAMHD1 expression is regulated.
authors: Center for Retrovirus Research, Department of Veterinary Biosciences, The OhioState University, Columbus, OH 43210, USA.
authors: Suresh
authors: S
authors: de Silva
authors: Heather
authors: H
authors: Hoy
authors: Timothy S
authors: TS
authors: Hake
authors: Henry K
authors: HK
authors: Wong
authors: Pierluigi
authors: P
authors: Porcu
authors: Li
authors: L
authors: Wu
mesh_terms: D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D049109:Cell Proliferation; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D000076106:SAM Domain and HD Domain-Containing Protein 1; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic
chemical_list: D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D020559:Monomeric GTP-Binding Proteins