Genetic and Molecular Analyses of PEG10 Reveal New Aspects of Genomic Organization, Transcription and Translation

Abstract

The paternally expressed gene PEG10 is a retrotransposon derived gene adapted through mammalian evolution located on human chromosome 7q21. PEG10 codes for at least two proteins, PEG10-RF1 and PEG10-RF1/2, by -1 frameshift translation. Overexpression or reinduced PEG10 expression was seen in malignancies, like hepatocellular carcinoma or B-cell acute and chronic lymphocytic leukemia. PEG10 was also shown to promote adipocyte differentiation. Experimental evidence suggests that the PEG10-RF1 protein is an inhibitor of apoptosis and mediates cell proliferation. Here we present new data on the genomic organization of PEG10 by identifying the major transcription start site, a new splice variant and report the cloning and analysis of 1.9 kb of the PEG10 promoter. Furthermore, we show for the first time that PEG10 translation is initiated at a non-AUG start codon upstream of the previously predicted AUG codon as well as at the AUG codon. The finding that PEG10 translation is initiated at different sides adds a new aspect to the already interesting feature of PEG10's −1 frameshift translation mechanism. It is now important to unravel the cellular functions of the PEG10 protein variants and how they are related to normal or pathological conditions. The generated promoter-reporter constructs can be used for future studies to investigate how PEG10 expression is regulated. In summary, our study provides new data on the genomic organization as well as expression and translation of PEG10, a prerequisite in order to study and understand the role of PEG10 in cancer, embryonic development and normal cell homeostasis.

Epigenetic modifications at DMRs of placental genes are subjected to variations in normal gestation, pathological conditions and folate supplementation

“…Such increased expression upon folic acid treatment in case of PEG10 , was observed only in choriocarcinomic JEG-3 cells, at lower folic acid supplementation while no such change was induced in extravillous HTR-8/SVneo cell line. Overexpression of PEG10 has earlier been correlated with various cancers such as B-cell lymphocytic leukemia and hepatocellular carcinoma39. Therefore, folic acid mediated increase in PEG10 expression, might be promoting malignancy like phenotype of placental development.…”

“…Any variation, lower or higher than the physiological level leads to placental disorders like preeclampsia and hydatiform mole, respectively. In this context, we intended to find the role of three paternally expressed genes: SNRPN , PEG10 and MEST , with known function in placental development and carcinogenesis383940. These genes are involved in mediating cell proliferation, invasion and growth, thus, highlighting their potential in tumor formation.…”

Expression and significance of the imprinted gene PEG10 in placenta of patients with preeclampsia

“…This indicates that the loss of PEG10 may be an important regulatory event in preeclampsia. Its mechanism may be that the loss of PEG10 induces apoptosis, and mediated by the method of siRNA, it led to increased cell apoptosis (Lux et al, 2010). Excessive expression of PEG10 -RF1 protein plays an anti-apoptosis role and promotes cell growth (Clark et al, 2007).…”

Specific changes in the expression of imprinted genes in prostate cancer—implications for cancer progression and epigenetic regulation

“…145 Due to the sharing of a common promoter, PEG10 and SGCE are often coexpressed, but in some cases their expression diverges. 146 The 7q21 cluster further contains the maternally expressed gene tissue factor pathway inhibitor 2 (TFPI2). It is considered as a tumour suppressor candidate, because it is silenced by genetic and epigenetic aberrations in several types of cancer, including prostate cancer.…”