Molecular and structural interactions between epigenetic regulators

The two major classes of proteins that preside over epigenetic mechanisms in the cells are DNA methyltransferases (DNMTs) and histone deacetylases (HDACs). Cellular proteins were identified that directly interact with these epigenetic regulators to initiate new molecular mechanisms or to alter the normal cellular pathways. During the growth and development of an organism, timely initiation and inhibition of epigenetic mechanisms is required. However, as identified in some of the disease conditions such as in proliferative disorders, abnormal initiation of epigenetic mechanisms was the causative factor for disease onset and progression. Understanding how the abnormal or untimely initiation of epigenetic mechanisms occurs, as well as the cellular proteins that initiate such disease-causing mechanisms, would greatly facilitate the treatment of the associated disease/disorder. Besides the interaction between the cellular proteins and epigenetic regulators, molecular interactions between different epigenetic regulators such as DNMTs and HDACs, and between different isoforms such as between HDAC1 and HDAC2, or between DNMT1 and DNMT3L, are also known. Considering the enormity of this topic, this chapter focuses on some of the most studied epigenetic regulators, DNMTs and HDACs. These two classes of epigenetic regulators have unique mechanisms of action. While DNMTs control epigenetic regulations by methylating DNA, HDAC proteins exert their epigenetic actions through deacetylation of amino acid residues on histone proteins that coil DNA. Although the functional mechanisms of these two types of epigenetic regulators are different, the end result of their actions is the same: affecting gene transcription.