Akademik Veri Yönetim Sistemi
Recent Insights into Molecular Biology and Genetics', Sevgi Maraklı,Merve Yılmazer, Editör, Gaziantep Üniversitesi Yayınları, Gaziantep, ss.41-84, 2023
Proteins undergo post-translational modifications to perform their functions. Acetylation is one of the well-known post-translational modifications of proteins. Histones associate with DNA to form the fundamental level of chromatin packaging and represent the most-studied targets of protein acetylation, which was discovered on histones. Acetylation occurs on and reduces the electrical charge of lysine moieties and is affected by the availability of acetyl-CoA, an essential metabolite in energy production in mitochondria. The presence of acetylated lysine marks the genes as active due to the weakening of the interaction between histones and DNA. In addition to serving as a chromatin modification, histone acetylation also regulates intracellular pH, which is frequently disturbed in cancer. Acetylation and deacetylation of histones are mediated by histone acetyltransferases (HATs) and histone deacetylases (HDACs) respectively, and determined by intracellular levels of acetyl-CoA. HATs and HDACs are known to be impaired in many types of cancer and several inhibitors have been utilized particularly in cancer therapy. As one of the hallmarks of cancer is the deregulated metabolism; acetyl-CoA production, metabolism, signaling and cancer are connected. In this chapter, we will describe the acetylation and deacetylation of histones, the enzymes responsible, and the molecules that modulate the enzymes. Then, we will briefly review the main epigenetic mechanisms involved in carcinogenesis. Next, we will cover the recent findings on how deregulated acetylation/deacetylation events contribute to cancer development and how epigenetic drugs that target histone acetylation, and exert their effects on cancer. Finally, ChIP-seq, a method for the analysis of histone acetylation, and its bioinformatic tools will be discussed shortly.