DNA hypermethylation in disease: mechanisms and clinical relevance

被引：267

作者：

Ehrlich, Melanie ^{[1
,2
]}

机构：

[1] Tulane Canc Ctr, SL31,JBJ 305,1430 Tulane Ave, New Orleans, LA 70122 USA

[2] Tulane Univ, Hlth Sci Ctr, Tulane Ctr Bioinformat & Genom, New Orleans, LA 70118 USA

来源：

EPIGENETICS | 2019年 / 14卷 / 12期

基金：

美国国家卫生研究院;

关键词：

DNA hypermethylation; cancer stem cells; CpG island methylator phenotype (CIMP); brain disease; immune dysfunction; osteoporosis; atherosclerosis; TET; DNMT; aging; SMOOTH-MUSCLE-CELLS; DE-NOVO METHYLATION; CPG ISLANDS; CYTOSINE MODIFICATIONS; COLORECTAL-CANCER; TUMOR-SUPPRESSOR; STEM-CELLS; HYPOMETHYLATION; CHROMATIN; 5-HYDROXYMETHYLCYTOSINE;

D O I：

10.1080/15592294.2019.1638701

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Increasing numbers of studies implicate abnormal DNA methylation in cancer and many non-malignant diseases. This is consistent with numerous findings about differentiation-associated changes in DNA methylation at promoters, enhancers, gene bodies, and sites that control higher-order chromatin structure. Abnormal increases or decreases in DNA methylation contribute to or are markers for cancer formation and tumour progression. Aberrant DNA methylation is also associated with neurological diseases, immunological diseases, atherosclerosis, and osteoporosis. In this review, I discuss DNA hypermethylation in disease and its interrelationships with normal development as well as proposed mechanisms for the origin of and pathogenic consequences of disease-associated hypermethylation. Disease-linked DNA hypermethylation can help drive oncogenesis partly by its effects on cancer stem cells and by the CpG island methylator phenotype (CIMP); atherosclerosis by disease-related cell transdifferentiation; autoimmune and neurological diseases through abnormal perturbations of cell memory; and diverse age-associated diseases by age-related accumulation of epigenetic alterations.

引用

页码：1141 / 1163

页数：23

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