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糖基化的表观遗传调控

Epigenetic Regulation of Glycosylation.

机构信息

Department of Health Sciences, University of Milan, Milan, Italy.

Department of Medicine and Surgery (DMC), University of Insubria, Varese, Italy.

出版信息

Adv Exp Med Biol. 2021;1325:173-186. doi: 10.1007/978-3-030-70115-4_8.

Abstract

Expression of glycosylation-related genes (or glycogenes) is strictly regulated by transcription factors and epigenetic processes, both in normal and in pathological conditions. In fact, glycosylation is an essential mechanism through which proteins and lipids are modified to perform a variety of biological events, to adapt to environment, and to interact with microorganisms.Many glycogenes with a role in normal development are epigenetically regulated. Essential studies were performed in the brain, where expression of glycogenes like MGAT5B, B4GALNT1, and ST8Sia1 are under the control of histone modifications, and in the immune system, where expression of FUT7 is regulated by both DNA methylation and histone modifications. At present, epigenetic regulation of glycosylation is still poorly described under physiological conditions, since the majority of the studies were focused on cancer. In fact, virtually all types of cancers display aberrant glycosylation, because of both genetic and epigenetic modifications on glycogenes. This is also true for many other diseases, such as inflammatory bowel disease, diabetes, systemic lupus erythematosus, IgA nephropathy, multiple sclerosis, and cardiovascular diseases.A deeper knowledge in epigenetic regulation of glycogenes is essential, since research in this field could be helpful in finding novel and personalized therapeutics.

摘要

糖基化相关基因(或糖基因)的表达受转录因子和表观遗传过程的严格调控,无论是在正常条件下还是在病理条件下。事实上,糖基化是一种重要的机制,通过该机制,蛋白质和脂质被修饰以执行各种生物事件,适应环境并与微生物相互作用。许多在正常发育中起作用的糖基因受到表观遗传调控。在大脑中进行了重要的研究,MGAT5B、B4GALNT1 和 ST8Sia1 等糖基因的表达受组蛋白修饰的控制,在免疫系统中,FUT7 的表达受 DNA 甲基化和组蛋白修饰的共同调控。目前,由于大多数研究都集中在癌症上,因此在生理条件下,对糖基化的表观遗传调控仍知之甚少。事实上,几乎所有类型的癌症都表现出异常的糖基化,这是由于糖基因的遗传和表观遗传修饰。许多其他疾病也是如此,如炎症性肠病、糖尿病、系统性红斑狼疮、IgA 肾病、多发性硬化症和心血管疾病。深入了解糖基因的表观遗传调控至关重要,因为该领域的研究可能有助于发现新的个性化治疗方法。

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