Cell lineage specificity in G-CSF receptor gene methylation.

In hematopoiesis the evolution of specialized cell lineages from a common stem cell is mediated by lineage-specific growth factors. The role of DNA methylation in the multilevel regulation of the differential gene expression, especially in the case of growth factor receptor genes, has remained elusive. In earlier studies we showed a lineage-specific methylation pattern of the M-CSF receptor gene c-fms in blood monocytes and tissue macrophages. Here, we provide evidence that a lineage-specific hypomethylation exists for the G-CSF receptor gene for myelomonocytic cells but not in lymphocytes without any interindividual differences. Constant differences were found between alveolar and peritoneal macrophages with a lesser degree of methylation in peritoneal macrophages. Acute myelomonocytic leukemias showed an increased methylation as compared with normal granulocytes and monocytes. All permanent cell lines analyzed revealed hypermethylation of the G-CSF receptor gene. Lymphocytes of B-CLL showed a strong hypermethylation of this gene. Increased methylation has been shown to be inversely correlated with transcriptional gene activities. We conclude that the methylation pattern of growth factor receptor genes may be one of the regulatory mechanisms in multi-lineage differentiation.