Epigenetic mechanisms such as DNA methylation and histone modifications that control gene expression are essential in the process of individual development and cell differentiation. Environmental factors (infection, inflammation, dysbiosis, nutritional composition, alcohol consumption, smoking, etc.) induce epigenetic changes, which sometimes cause aberrant gene expression without changing the DNA sequence [1]. These changes are maintained after cell division and are eventually involved in the onset and progression of diseases [2]. Many glyco-genes are involved in the synthesis of carbohydrate antigens. It has been reported that the brain-specific expression of N-acetylglucosaminyltransferase-IX (GnT-IX) gene is epigenetically regulated by specific histone modifications [3]. This result suggests that epigenetic modifications of glycosyltransferases may play an important role in tissue-specific expression of carbohydrate antigens. Previous studies revealed increased DNA methylation in the promoter regions of glycosyltransferases, which inhibit the synthesis of tumor-related carbohydrate antigens by competing for substrates [4]. Therefore, to clarify the epigenetic mechanism, regulating glyco-genes is important for understanding the tissue- and disease-specific expression of carbohydrate antigens (Fig. 50.1).