Fig. 2

Epigenetic changes in routine and tumor cells in breast cancer. Epigenetic modifications such as DNA methylation and histone modification alter DNA accessibility and chromatin structure, thereby regulating patterns of gene expression. In normal cells, DNA methyltransferases (DNMTs) add a methyl group at position 5 of the pyrimidine ring of cytosine, which is known as DNA methylation. The Ten Eleven Translocation (TET) family of proteins catalyze the subsequent oxidations of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). TET proteins therefore provide an active pathway for DNA demethylation and consequently have relevance for regulation of gene expression. TET proteins can also mediate active demethylation via excision of 5fC and 5caC by thymine DNA glycosylase (TDG). Additionally, histone acetyltransferases (HATs) acetylate conserved lysine amino acids on histone proteins by transferring an acetyl group from acetyl-CoA to form ε-N-acetyllysine. Also, the methylation of histone H3 at lysine 27 (H3K27me1/2/3) is catalyzed by polycomb repressive complex 2 (PRC2)—which is a chromatin-modifying enzyme. Moreover, both gene transcriptional repression and normal organismal development can be maintained by this complex. Nonetheless, cancer cells have a different epigenetic profile. Decreased methylation was seen in the epigenetic profile of cancer cells. This decreased methylation can affect the activity of large numbers of genes. Since methylation has been linked with decreased gene activity, the implication of hypomethylation is to escalate the activity of the affected genes. In this condition, if genes involved are in cell growth, this event can result in cell division and, thus, cancer progression. In addition, increased activity of histone deacetylases (HDACs) has been found in different types of cancer cells such as breast cancer, and it is marked by a loss of histone acetyl markers. Histone methyltransferases (HMTs) are enzymes that add methyl groups to histones, while histone demethylases (HDMs) have the inverse function. In breast cancer cells, HMTs may be altered so that they place methyl groups at the wrong spot, thereby silencing tumor suppressor genes. All these events as well as mutation of SWI/SNF chromatin remodeling complex subunits can lead to abnormal chromatin structure, contributing to cancer development