Dynamic DNA methylation change in the CpG island region of p15 during human myeloid development
| Autor: | K, Sakashita, K, Koike, T, Kinoshita, M, Shiohara, T, Kamijo, S, Taniguchi, T, Kubota |
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| Rok vydání: | 2001 |
| Předmět: |
Molecular Sequence Data
Gene Expression Antigens CD34 Cell Cycle Proteins Article Colony-Forming Units Assay Humans Genes Tumor Suppressor Promoter Regions Genetic Alleles Cells Cultured Cyclin-Dependent Kinase Inhibitor p16 Cyclin-Dependent Kinase Inhibitor p15 Stem Cell Factor Base Sequence Macrophages Tumor Suppressor Proteins Granulocyte-Macrophage Colony-Stimulating Factor DNA General Medicine DNA Methylation Fetal Blood Hematopoietic Stem Cells Hematopoiesis Kinetics CpG Islands Granulocytes |
| Zdroj: | Journal of Clinical Investigation. 108:1195-1204 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci200113030 |
| Popis: | We examined the kenetics of p15 methylation and expression during myeloid development. We treated human cord blood CD34+ cells with either GM-CSF alone or in combination with stem cell factor and followed methylation at this locus using bisulfite genomic sequencing. CD34+ cells were found to be either fully methylated or completely unmethylated at 27 CpG dinucleotide sites in exon 1 and at 18 CpG sites in the promoter region of the p15 gene. A time-course study showed that the percentage of the allelic methylation of p15 CpG island increased to approximately 50% to 60% until 7 days after cytokine stimulation, then decreased to less than 10% after 21 days. The methylation was also observed in bone marrow CD34+ cells exposed to GM-CSF. p15 expression varied inversely with methylation. Expression was negligible or at low levels until 14 days, after which it increased substantially. The frequency of myeloid colony-forming cells in the progeny decreased and myeloid-specific markers increased in the later stages. Based on our observations on cells grown with GM-CSF and 5-aza-2′-deoxycytidine, DNA methylation of the p15 promoter region CpG island appears to be associated with proliferation rather than differentiation of normal human myeloid progenitors. |
| Databáze: | OpenAIRE |
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