Differential patterns of methylation of the IFN promoter at CpG and non-CpG sites underlie differences in IFN gene expression between human neonatal and adult CD45RO- T-cells
IFN- is a potent pleiotropic Th1 cytokine, the production of which is tightly regulated during fetal development. Negative control of fetal/neonatal IFN- production is generally attributed to the Th1-antagonistic effect of mediators produced by the placenta, but evidence exists of additional and mor...
| Main Authors: | , , , |
|---|---|
| Format: | Journal Article |
| Published: |
American Association of Immunologists
2002
|
| Online Access: | http://www.jimmunol.org/cgi/content/abstract/168/6/2820 http://hdl.handle.net/20.500.11937/24398 |
| _version_ | 1848751417310838784 |
|---|---|
| author | White, Greg Watt, P. Holt, B. Holt, P. |
| author_facet | White, Greg Watt, P. Holt, B. Holt, P. |
| author_sort | White, Greg |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | IFN- is a potent pleiotropic Th1 cytokine, the production of which is tightly regulated during fetal development. Negative control of fetal/neonatal IFN- production is generally attributed to the Th1-antagonistic effect of mediators produced by the placenta, but evidence exists of additional and more direct transcriptional regulation. We report that neonatal (cord blood) CD3+/CD45RO- T cells, in particular the CD4+/CD45RO- subset, are hypermethylated at CpG and non-CpG (CpA and CpT) sites within and adjacent to the IFN- promoter. In contrast, CpG methylation patterns in cord blood IFN--producing CD8+/CD45RO- T cells and CD56+/CD16+/CD3- NK cells did not differ significantly from those in their adult counterparts. Consistent with this finding, IFN- production by stimulated naive cord blood CD4+ T cells is reduced 5- to 10-fold relative to adult CD4+ T cells, whereas production levels in neonatal and adult CD8+ T cells are of a similar order. Evidence of significant CpA and CpT methylation was not discovered in promoter sequence from other cytokines (IL-4, TNF-, or IFN-R -chain). We additionally demonstrate that overexpression of DNA methyltransferase 3a in embryonic kidney carcinoma cells is accompanied by CpA methylation of the IFN- promoter |
| first_indexed | 2025-11-14T07:52:24Z |
| format | Journal Article |
| id | curtin-20.500.11937-24398 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T07:52:24Z |
| publishDate | 2002 |
| publisher | American Association of Immunologists |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-243982018-12-14T00:51:47Z Differential patterns of methylation of the IFN promoter at CpG and non-CpG sites underlie differences in IFN gene expression between human neonatal and adult CD45RO- T-cells White, Greg Watt, P. Holt, B. Holt, P. IFN- is a potent pleiotropic Th1 cytokine, the production of which is tightly regulated during fetal development. Negative control of fetal/neonatal IFN- production is generally attributed to the Th1-antagonistic effect of mediators produced by the placenta, but evidence exists of additional and more direct transcriptional regulation. We report that neonatal (cord blood) CD3+/CD45RO- T cells, in particular the CD4+/CD45RO- subset, are hypermethylated at CpG and non-CpG (CpA and CpT) sites within and adjacent to the IFN- promoter. In contrast, CpG methylation patterns in cord blood IFN--producing CD8+/CD45RO- T cells and CD56+/CD16+/CD3- NK cells did not differ significantly from those in their adult counterparts. Consistent with this finding, IFN- production by stimulated naive cord blood CD4+ T cells is reduced 5- to 10-fold relative to adult CD4+ T cells, whereas production levels in neonatal and adult CD8+ T cells are of a similar order. Evidence of significant CpA and CpT methylation was not discovered in promoter sequence from other cytokines (IL-4, TNF-, or IFN-R -chain). We additionally demonstrate that overexpression of DNA methyltransferase 3a in embryonic kidney carcinoma cells is accompanied by CpA methylation of the IFN- promoter 2002 Journal Article http://hdl.handle.net/20.500.11937/24398 http://www.jimmunol.org/cgi/content/abstract/168/6/2820 American Association of Immunologists restricted |
| spellingShingle | White, Greg Watt, P. Holt, B. Holt, P. Differential patterns of methylation of the IFN promoter at CpG and non-CpG sites underlie differences in IFN gene expression between human neonatal and adult CD45RO- T-cells |
| title | Differential patterns of methylation of the IFN promoter at CpG and non-CpG sites underlie differences in IFN gene expression between human neonatal and adult CD45RO- T-cells |
| title_full | Differential patterns of methylation of the IFN promoter at CpG and non-CpG sites underlie differences in IFN gene expression between human neonatal and adult CD45RO- T-cells |
| title_fullStr | Differential patterns of methylation of the IFN promoter at CpG and non-CpG sites underlie differences in IFN gene expression between human neonatal and adult CD45RO- T-cells |
| title_full_unstemmed | Differential patterns of methylation of the IFN promoter at CpG and non-CpG sites underlie differences in IFN gene expression between human neonatal and adult CD45RO- T-cells |
| title_short | Differential patterns of methylation of the IFN promoter at CpG and non-CpG sites underlie differences in IFN gene expression between human neonatal and adult CD45RO- T-cells |
| title_sort | differential patterns of methylation of the ifn promoter at cpg and non-cpg sites underlie differences in ifn gene expression between human neonatal and adult cd45ro- t-cells |
| url | http://www.jimmunol.org/cgi/content/abstract/168/6/2820 http://hdl.handle.net/20.500.11937/24398 |