Metabolic Diseases Downregulate the Majority of Histone Modification Enzymes, Making a Few Upregulated Enzymes Novel Therapeutic Targets—“Sand Out and Gold Stays”

• DOI: 10.1007/s12265-015-9664-y
• Publication Date: 2016-01-08T09:49:17Z
• Authors: Ying Shao; Valeria Chernaya; Candice Johnson; William Y. Yang; Ramon Cueto; Xiaojin Sha; Yi Zhang; Xuebin Qin; Jianxin Sun; Eric T. Choi; Hong Wang; Xiao-feng Yang
• Keywords: Histone Methylation; Vorinostat

To determine whether the expression of histone modification enzymes is regulated in physiological and pathological conditions, we took an experimental database mining approach pioneered in our labs to determine a panoramic expression profile of 164 enzymes in 19 human and 17 murine tissues. We have made the following significant findings: (1) Histone enzymes are differentially expressed in cardiovascular, immune, and other tissues; (2) our new pyramid model showed that heart and T cells are among a few tissues in which histone acetylation/deacetylation, and histone methylation/demethylation are in the highest varieties; and (3) histone enzymes are more downregulated than upregulated in metabolic diseases and regulatory T cell (Treg) polarization/ differentiation, but not in tumors. These results have demonstrated a new working model of "Sand out and Gold stays," where more downregulation than upregulation of histone enzymes in metabolic diseases makes a few upregulated enzymes the potential novel therapeutic targets in metabolic diseases and Treg activity.