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Epigenetic Memory, Melanoma Antigen Genes (MAGEs) and Cancer
Author(s) -
Ramanathan Saumya,
Colemon Ashley,
Harris Taylor,
Jackson Richala
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.621.11
Subject(s) - epigenetics , dna methylation , biology , gene , promoter , germline , genetics , dna methyltransferase , gene expression , cancer research
Melanoma Antigen Genes (MAGEs) are a family of tumor‐associated genes. MAGE‐A, ‐B and ‐C genes belong to the Type I MAGE subfamily. They are typically expressed in the male germline and then aberrantly expressed in many cancers. Their expression in tumors is often associated with poor patient prognosis. There is a significant gap in understanding the mechanisms that regulate the expression of Type I MAGE genes is regulated. Cancers often express more than one MAGE gene and for this reason we hypothesized that epigenetic mechanisms such as DNA methylation, which regulates the expression of many germline genes also regulates MAGE gene expression. Using DNA methyltransferase (DNMT) inhibitors and bioinformatics analysis of MAGE‐A gene promoters, we have determined that while CpG methylation does regulate gene expression, remarkably, when “normal” cells are threatened with toxins and DNA damage they resort to expressing the MAGE genes. In addition, we show that expressing MAGE‐A genes provides non‐transformed cells with a proliferative advantage. Taken together our data indicate that cells use epigenetic memory to express MAGE‐A genes resulting in shift of the cells' gene signature to a pro‐proliferative, anti‐apoptotic state that firmly places cells in the path to transformation. Support or Funding Information NSF Research Initiation Award HRD1764201 to S.R.NSF Implementation Award HRD1332284 Fisk University Implementation Award NIH R25 Bridge to the Doctorate Grant‐1R25GM107754Graphical AbstractThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .