Cell lineage specificity in G-CSF receptor gene methylation

In hematopoiesis the evolution of specialized cell lineages from a common s tem cell is mediated by lineage-specific growth factors. The role of DNA me thylation in the multilevel regulation of the differential gene expression, especially in the case of growth factor receptor genes, has remained elusi ve. In earlier studies we showed a lineage-specific methylation pattern of the M-CSF receptor gene c-fms in blood monocytes and tissue macrophages. He re, we provide evidence that a lineage-specific hypomethylation exists for the G-CSF receptor gene for myelomonocytic cells but not in lymphocytes wit hout any interindividual differences. Constant differences were found betwe en alveolar and peritoneal macrophages with a lesser degree of methylation in peritoneal macrophages. Acute myelomonocytic leukemias showed an increas ed methylation as compared with normal granulocytes and monocytes. All perm anent cell lines analyzed revealed hypermethylation of the G-CSF receptor g ene. Lymphocytes of B-CLL showed a strong hypermethylation of this gene. In creased methylation has been shown to be inversely correlated with transcri ptional gene activities. We conclude that the methylation pattern of growth factor receptor genes may be one of the regulatory mechanisms in multi-lin eage differentiation.