Ludwig Institute for Cancer Research, La Jolla, CA, USA.
Center for Epigenomics, University of California, San Diego School of Medicine, La Jolla, CA, USA.
Nature. 2020 Jul;583(7818):744-751. doi: 10.1038/s41586-020-2093-3. Epub 2020 Jul 29.
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.
DNA 元件百科全书 (ENCODE) 项目建立了一个哺乳动物发育的基因组资源，对从受孕后 10.5 天到出生的 8 个发育阶段的多种小鼠组织进行了全面分析，包括转录组、甲基组和染色质状态。在这里，我们系统地研究了发育中胎儿小鼠染色质的状态和可及性。我们总共进行了 1128 次染色质免疫沉淀测序 (ChIP-seq) 检测，用于检测组蛋白修饰，以及 132 次转座酶可及染色质测序 (ATAC-seq) 检测，用于检测染色质可及性，这些检测跨越了 72 个不同的组织阶段。我们使用整合分析方法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节因子的身份，并描述发育过程中基因调控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潜在的靶基因联系起来，并证明与人类疾病相关的序列变异在特定组织中富集。这些小鼠 ENCODE 数据集为生物医学研究人员提供了一个资源总库，据我们所知，这是迄今为止对哺乳动物胎儿发育过程中染色质动态的最全面观察。
