Epigenetic regulation in human brain-focus on histone lysine methylation.
Epigenetic regulation in human brain-focus on histone lysine methylation.
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组蛋白赖氨酸甲基化对人脑焦点的表观遗传调节。
DOI：
10.1016/j.biopsych.2008.08.015
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发表时间：
2009-02-01
影响因子：
10.6
通讯作者：
Huang, Hsien-Sung
中科院分区：
文献类型：
--
作者：
Akbarian, Schahram;Huang, Hsien-Sung
在被诊断为自闭症、精神分裂症、抑郁症和其他精神疾病的受试者中，RNA水平的变化经常被报道，但目前尚不清楚潜在的分子病理是否涉及基因表达的变化，而不是mRNA加工的变化。临床前研究表明，应激、药物和其他各种环境因素通过表观遗传机制，包括组蛋白修饰，导致脑内RNA水平的变化。核小体核心组蛋白的一些位点特异性修饰-包括组蛋白H3赖氨酸K4、K9和K27的三甲基化形式-对尸检研究特别感兴趣，因为这些标记区分活性和非活性染色质，并且在组织自溶期间似乎保持相对稳定。因此，启动子区域的组蛋白甲基化分析可以为人类大脑发育和疾病中基因表达的机制提供重要线索。有趣的是，编码H3K9特异性甲基转移酶EHMT1和H3K4特异性组蛋白去甲基酶JARID1C/SMCX的基因突变分别与智力低下和自闭症有关。此外，H3K4特异性甲基转移酶MLL1对海马区突触可塑性至关重要，可能与某些精神分裂症患者的皮质功能障碍有关。总之，这些发现强调了组蛋白赖氨酸甲基化对大脑有序发育的潜在意义，也是研究死后组织染色质功能的分子工具箱。
Alterations in RNA levels are frequently reported in brain of subjects diagnosed with autism, schizophrenia, depression and other psychiatric diseases, but it remains unclear whether the underlying molecular pathology involves changes in gene expression, as opposed to alterations in mRNA processing. Pre-clinical studies have revealed that stress, drugs, and a variety of other environmental factors lead to changes in RNA levels in brain via epigenetic mechanisms, including modification of histone proteins. A number of site-specific modifications of the nucleosome core histones—including the trimethylated forms of histone H3 lysines K4, K9, and K27—are of particular interest for postmortem research, because these marks differentiate between active and inactive chromatin, and appear to remain relatively stable during tissue autolysis. Therefore, histone methylation profiling at promoter regions could provide important clues about mechanisms of gene expression in human brain during development and in disease. Intriguingly, mutations within the genes encoding the H3K9-specific methyltransferase, EHMT1, and the H3K4-specific histone demethylase, JARID1C/SMCX, have been linked to mental retardation and autism, respectively. In addition, the H3K4-specific methyltransferase, MLL1, is essential for hippocampal synaptic plasticity and may be involved in cortical dysfunction of some cases of schizophrenia. Together, these findings emphasize the potential significance of histone lysine methylation for orderly brain development and also as a molecular toolbox to study chromatin function in postmortem tissue.
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影响因子：
--
作者：
Akbarian, S;Ruehl, MG;Guo, Y
通讯作者：
Guo, Y
影响因子：
2
作者：
Adegbola, Abidemi;Gao, Hanlin;Browning, Marsha
通讯作者：
Browning, Marsha
影响因子：
64.5
作者：
Guenther, Matthew G.;Levine, Stuart S.;Young, Richard A.
通讯作者：
Young, Richard A.
影响因子：
5.3
作者：
Huang, Hsien-Sung;Matevossian, Anouch;Akbarian, Schahram
通讯作者：
Akbarian, Schahram
影响因子：
2.7
作者：
Biron, VL;McManus, KJ;Underhill, DA
通讯作者：
Underhill, DA