Mendelian disorders of the epigenetic machinery: tipping the balance of chromatin states.
Mendelian disorders of the epigenetic machinery: tipping the balance of chromatin states.
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DOI：
10.1146/annurev-genom-090613-094245
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发表时间：
2014
影响因子：
8.7
通讯作者：
Bjornsson HT
中科院分区：
文献类型：
--
作者：
Fahrner JA;Bjornsson HT
表观遗传机制的孟德尔疾病是一组新划定的多重先天性异常和智力残疾综合征，由表观遗传机制的基因编码组分突变引起。在这些遗传条件下受影响的基因产物以反式方式起作用，预计会产生广泛的表观遗传后果。许多这些综合征表现出与经典的印记疾病和彼此的表型重叠。不同的写入器和擦除器系统涉及对立的参与者，我们认为它们必须在任何给定的细胞中保持开放和封闭染色质状态之间的平衡。失衡可能导致疾病相关靶基因的表达中断。我们认为，分类疾病的基础上预测的影响，这种平衡将是信息的发病机制。此外，针对恢复这种平衡的策略可能会提供新的治疗途径，利用现有的药物，如组蛋白去乙酰化酶抑制剂和组蛋白乙酰化拮抗剂。
Mendelian disorders of the epigenetic machinery are a newly delineated group of multiple congenital anomaly and intellectual disability syndromes resulting from mutations in genes encoding components of the epigenetic machinery. The gene products affected in these inherited conditions act in trans and are expected to have widespread epigenetic consequences. Many of these syndromes demonstrate phenotypic overlap with classical imprinting disorders and with one another. The various writer and eraser systems involve opposing players, which we propose must maintain a balance between open and closed chromatin states in any given cell. An imbalance might lead to disrupted expression of disease-relevant target genes. We suggest that classifying disorders based on predicted effects on this balance would be informative regarding pathogenesis. Furthermore, strategies targeted at restoring this balance might offer novel therapeutic avenues, taking advantage of available agents such as histone deacetylase inhibitors and histone acetylation antagonists.
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影响因子：
3.7
作者：
Buck-Koehntop BA;Defossez PA
通讯作者：
Defossez PA
DOI：
10.1038/nrclinonc.2013.42
发表时间：
2013-05
期刊：
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发表时间：
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期刊：
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影响因子：
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作者：
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通讯作者：
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影响因子：
64.8
作者：
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通讯作者：
Kouzarides, T