Journal article
Promoter Methylation Regulates SAMHD1 Gene Expression in Human CD4+ T Cells
The Journal of biological chemistry, Vol.288(13), pp.9284-9292
03/29/2013
DOI: 10.1074/jbc.M112.447201
PMCID: PMC3610999
PMID: 23426363
Abstract
Background:
SAMHD1 expression is significantly reduced in CD4
+
T cell lines compared with primary CD4
+
T lymphocytes.
Results:
The
SAMHD1
promoter contains a CpG island that is prone to DNA methylation.
Conclusion:
Methylation of the
SAMHD1
promoter contributes to transcriptional repression in CD4
+
T cell lines.
Significance:
We identified promoter methylation as a contributing factor to
SAMHD1
gene regulation.
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.
Details
- Title: Subtitle
- Promoter Methylation Regulates SAMHD1 Gene Expression in Human CD4+ T Cells
- Creators
- Suresh de Silva - Center for Retrovirus Research, Department of Veterinary BiosciencesHeather Hoy - Center for Retrovirus Research, Department of Veterinary BiosciencesTimothy S Hake - Comprehensive Cancer Center, andHenry K Wong - Dermatology andPierluigi Porcu - Hematology, The Ohio State University, Columbus, Ohio 43210Li Wu - Comprehensive Cancer Center, and
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.288(13), pp.9284-9292
- DOI
- 10.1074/jbc.M112.447201
- PMID
- 23426363
- PMCID
- PMC3610999
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- American Society for Biochemistry and Molecular Biology; 9650 Rockville Pike, Bethesda, MD 20814, U.S.A
- Grant note
- AI098524; AI102822 / National Institutes of Health
- Alternative title
- SAMHD1 Promoter Regulation by CpG Methylation
- Language
- English
- Date published
- 03/29/2013
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984001120802771
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