Figure 1: Five mechanisms for epigenetic alterations in breast cancers. Each alteration involves many enzymes but the main players to cause methylation or acetylation are shown by arrows. These are not separate mechanisms and the enzymes do not act alone. Several enzymes act at a promoter simultaneously. (1) Hypermethylation at the CpG islands found in estrogen response element (ERE) promoters. When ligand- (L-) bonded ERα dimerizes, the complex (L-ERα dimer) acts as transcription factor and binds to the ERE promoter. Ligands could be E2, phytoestrogen, PhIP, and so forth. The dimer may recruit DNMTs which catalyze the transfer of methyl groups from SAM to 5′-cytosine on CpG islands. (2) Other enzymes could be recruited to the region by L-ERα dimers which activate DNA demethylases to act simultaneously to increase gene expression of protooncogenes and genes involved in cell growth. (3) L-ERα dimer may also recruit SWI/SNF and HATs to the ERE promoter region. HATs include p160, CBP, p300, pCAF. (4) Histone demethylases such as JMJD2B and (5) histone methyltransferases (HMTs) are enzymes which acetylate lysine residues on H3 and or H4 to open up the chromatin for other transcription factors and enzymes. Enzymes/cofactors: DNA methyltransferases (DNMTs), s-adenosylmethionine (SAM), histone acetyltransferases (HATs), histone methylases (HDM) JMJD2B, histone methyltransferases (HMTs), and DNA demethylases (member of MBD, methyl CpG-binding domain, family proteins).