Chromatin deregulation in disease
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- 作者：Anne C. Mirabella ; Benjamin M. Foster ; Till Bartke
- 关键词：Gene expression ; Epigenetics ; Chromatin ; DNA methylation ; Histone modifications ; Chromatin remodeling
- 刊名：Chromosoma
- 出版年：2016
- 出版时间：March 2016
- 年：2016
- 卷：125
- 期：1
- 页码：75-93
- 全文大小：1,143 KB
- 刊物类别：Biomedical and Life Sciences
- 刊物主题：Life Sciences
Cell Biology
Developmental Biology
Biochemistry
Human Genetics
Animal Genetics and Genomics
Eukaryotic Microbiology - 出版者：Springer Berlin / Heidelberg
- ISSN：1432-0886
文摘
The regulation of chromatin by epigenetic mechanisms plays a central role in gene expression and is essential for development and maintenance of cell identity and function. Aberrant chromatin regulation is observed in many diseases where it leads to defects in epigenetic gene regulation resulting in pathological gene expression programmes. These defects are caused by inherited or acquired mutations in genes encoding enzymes that deposit or remove DNA and histone modifications and that shape chromatin architecture. Chromatin deregulation often results in neurodevelopmental disorders and intellectual disabilities, frequently linked to physical and developmental abnormalities, but can also cause neurodegenerative diseases, immunodeficiency, or muscle wasting syndromes. Epigenetic diseases can either be of monogenic origin or manifest themselves as complex multifactorial diseases such as in congenital heart disease, autism spectrum disorders, or cancer in which mutations in chromatin regulators are contributing factors. The environment directly influences the epigenome and can induce changes that cause or predispose to diseases through risk factors such as stress, malnutrition or exposure to harmful chemicals. The plasticity of chromatin regulation makes targeting the enzymatic machinery an attractive strategy for therapeutic intervention and an increasing number of small molecule inhibitors against a variety of epigenetic regulators are in clinical use or under development. In this review, we will give an overview of the molecular lesions that underlie epigenetic diseases, and we will discuss the impact of the environment and prospects for epigenetic therapies.