An atlas of dynamic chromatin landscapes in mouse fetal development
An atlas of dynamic chromatin landscapes in mouse fetal development
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DOI：
10.1038/s41586-020-2093-3
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发表时间：
2020-07-30
期刊：
影响因子：
64.8
通讯作者：
Ren, Bing
中科院分区：
文献类型：
--
作者：
Gorkin, David U.;Barozzi, Iros;Ren, Bing
DNA元件百科全书（ENCODE）项目建立了哺乳动物发育的基因组资源，分析了从受孕后10.5天到出生的8个发育阶段的不同小鼠组织，包括转录组、甲基化组和染色质状态。在这里，我们系统地检查了状态和染色质的可及性在发育中的小鼠胎儿。我们总共进行了1，128次染色质免疫沉淀测序（ChIP-seq）试验，用于组蛋白修饰，并使用测序（ATAC-seq）试验进行了132次转座酶可及染色质试验，用于72个不同组织阶段的染色质可及性。我们使用综合分析开发了一套统一的染色质状态注释，推断动态增强子和关键转录调控因子的身份，并表征了发育基因调控过程中染色质状态和可及性之间的关系。我们还利用这些数据将增强子与推定的靶基因联系起来，并证明了与人类疾病相关的序列变异的组织特异性富集。小鼠ENCODE数据集为生物医学研究人员提供了一个资源纲要，并据我们所知，迄今为止，哺乳动物胎儿发育期间染色质动态的最全面的观点。
Analysis of chromatin state and accessibility in mouse tissues from twelve sites and eight developmental stages provides a comprehensive view of chromatin dynamics.The Encyclopedia of DNA Elements (ENCODE) project has established a genomic resource for mammalian development, profiling a diverse panel of mouse tissues at 8 developmental stages from 10.5 days after conception until birth, including transcriptomes, methylomes and chromatin states. Here we systematically examined the state and accessibility of chromatin in the developing mouse fetus. In total we performed 1,128 chromatin immunoprecipitation with sequencing (ChIP-seq) assays for histone modifications and 132 assay for transposase-accessible chromatin using sequencing (ATAC-seq) assays for chromatin accessibility across 72 distinct tissue-stages. We used integrative analysis to develop a unified set of chromatin state annotations, infer the identities of dynamic enhancers and key transcriptional regulators, and characterize the relationship between chromatin state and accessibility during developmental gene regulation. We also leveraged these data to link enhancers to putative target genes and demonstrate tissue-specific enrichments of sequence variants associated with disease in humans. The mouse ENCODE data sets provide a compendium of resources for biomedical researchers and achieve, to our knowledge, the most comprehensive view of chromatin dynamics during mammalian fetal development to date.