Shao Ying, Chernaya Valeria, Johnson Candice, Yang William Y, Cueto Ramon, Sha Xiaojin, Zhang Yi, Qin Xuebin, Sun Jianxin, Choi Eric T, Wang Hong, Yang Xiao-feng
Centers for Metabolic Disease Research, Cardiovascular Research & Thrombosis Research, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, 19140, USA.
Fels Institute for Cancer Research & Molecular Biology, Temple University School of Medicine, Philadelphia, PA, 19140, USA.
J Cardiovasc Transl Res. 2016 Feb;9(1):49-66. doi: 10.1007/s12265-015-9664-y. Epub 2016 Jan 8.
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.
为了确定组蛋白修饰酶的表达在生理和病理条件下是否受到调控，我们采用了在我们实验室开创的实验数据库挖掘方法，以确定164种酶在19种人类组织和17种小鼠组织中的全景表达谱。我们有以下重要发现：（1）组蛋白酶在心血管、免疫和其他组织中差异表达；（2）我们新的金字塔模型表明，心脏和T细胞是组蛋白乙酰化/去乙酰化以及组蛋白甲基化/去甲基化种类最多的少数组织之一；（3）在代谢疾病和调节性T细胞（Treg）极化/分化中，组蛋白酶下调多于上调，但在肿瘤中并非如此。这些结果展示了一种“沙汰金留”的新工作模式，即在代谢疾病中组蛋白酶下调多于上调，使得少数上调的酶成为代谢疾病和Treg活性潜在的新型治疗靶点。
