Tumor Suppressor Activity of Human Imprinted Gene PEG3 in Glioma Cells

Fumitoshi Ishino
Gene Research Center; Tokyo Institute of Technology

By systematic screening of imprinted genes the mouse using subtraction-hybridization technique comparing parthenogenetic embryos or androgenetic embryos with normal fertilized embryos, we have isolated 8 paternally expressed imprinted genes, Peg1-8, and 5 maternally expressed imprinted genes, Meg1-5. Mouse Peg3 is a paternally expressed imprinted gene that encodes for a large C2112 type zinc finger protein with unique characteristics. It is expressed in mesodermal tissues during embryogenesis and a high level of expression is observed in the central nervous system in adult. Recently, Peg3 knockout mice were found to show growth retardation before birth, as well as impairment of maternal behavior of the adult female that frequently resulted in death of the offspring. Therefore, it is important to examine the biochemical and cell biological functions of Peg3 gene at the cellular level.

Human PEG3 encodes a large zinc finger protein similar to mouse Peg3 and is also expressed in the adult brain. Peg3 protein was localized in the cell nuclei of both neurons and glial cells. The human PEG3 is located on the long arm of human chromosome 19, loss of heterozygosity of which occurs frequently and specifically in gliomas. Interestingly, the expression of PEG3 was greatly reduced and aberrant DNA methylation frequently occurred in some gliomas. Moreover, loss of tumorigenic activities of glioma cell lines was observed by introduction of the complete PEG3 cDNA (Genes to Cells, in press).