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DNA hypomethylation drives changes in MAGE-A gene expression resulting in alteration of proliferative status of cells.

Genes and environment : the official journal of the Japanese Environmental Mutagen Society (2020-08-08)
Ashley Colemon, Taylor M Harris, Saumya Ramanathan
ABSTRACT

Melanoma Antigen Genes (MAGEs) are a family of genes that have piqued the interest of scientists for their unique expression pattern. A subset of MAGEs (Type I) are expressed in spermatogonial cells and in no other somatic tissue, and then re-expressed in many cancers. Type I MAGEs are often referred to as cancer-testis antigens due to this expression pattern, while Type II MAGEs are more ubiquitous in expression. This study determines the cause and consequence of the aberrant expression of the MAGE-A subfamily of cancer-testis antigens. We have discovered that MAGE-A genes are regulated by DNA methylation, as revealed by treatment with 5-azacytidine, an inhibitor of DNA methyltransferases. Furthermore, bioinformatics analysis of existing methylome sequencing data also corroborates our findings. The consequence of expressing certain MAGE-A genes is an increase in cell proliferation and colony formation and resistance to chemo-therapeutic agent 5-fluorouracil and DNA damaging agent sodium arsenite. Taken together, these data indicate that DNA methylation plays a crucial role in regulating the expression of MAGE-A genes which then act as drivers of cell proliferation, anchorage-independent growth and chemo-resistance that is critical for cancer-cell survival.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
5-Fluorouracil, ≥99% (HPLC), powder
Sigma-Aldrich
Sodium (meta)arsenite, ≥90%
Sigma-Aldrich
5-Azacytidine, ≥98% (HPLC)