The epigenomic landscape regulating organogenesis in human embryos linked to developmental disorders
The epigenomic landscape regulating organogenesis in human embryos linked to developmental disorders
复制标题
调节与发育障碍相关的人类胚胎器官发生的表观基因组景观
DOI：
10.1101/691766
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Gerrard D
中科院分区：
文献类型：
--
作者：
Gerrard D
基因组如何激活或沉默转录程序控制器官的形成。在人类胚胎中，我们所知甚少，这削弱了我们对体外干细胞分化或细胞编程的保真度进行基准测试的能力，或者解释非编码变异的致病性。在这里，我们研究了人类器官发生过程中13种组织的组蛋白修饰。我们将数据与转录结合起来，首次概述了人类基因组如何通过抑制等方式差异调节替代器官的命运。来自近20，000个基因的启动子分配成离散状态，而不显示二价。关键的发育基因集在适当的器官外被积极抑制。候选增强子，功能在斑马鱼，允许插补的组织特异性和共享模式的转录因子结合。叠加来自发育障碍患者的700多个非编码突变，可以与意料之外的靶基因相关。总之，这些数据为研究正常和异常的人类发育提供了一个新的，全面的基因组框架。
How the genome activates or silences transcriptional programmes governs organ formation. Little is known in human embryos undermining our ability to benchmark the fidelity of in vitro stem cell differentiation or cell programming, or interpret the pathogenicity of noncoding variation. Here, we studied histone modifications across thirteen tissues during human organogenesis. We integrated the data with transcription to build the first overview of how the human genome differentially regulates alternative organ fates including by repression. Promoters from nearly 20,000 genes partitioned into discrete states without showing bivalency. Key developmental gene sets were actively repressed outside of the appropriate organ. Candidate enhancers, functional in zebrafish, allowed imputation of tissue-specific and shared patterns of transcription factor binding. Overlaying more than 700 noncoding mutations from patients with developmental disorders allowed correlation to unanticipated target genes. Taken together, the data provide a new, comprehensive genomic framework for investigating normal and abnormal human development.
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影响因子：
7
作者：
Siepel, A;Bejerano, G;Haussler, D
通讯作者：
Haussler, D
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通讯作者：
Kellis M