Chromatin accessibility dynamics reveal novel functional enhancers in C. elegans
Chromatin accessibility dynamics reveal novel functional enhancers in C. elegans
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DOI：
10.1101/gr.226233.117
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发表时间：
2017-12-01
期刊：
影响因子：
7
通讯作者：
Brunet, Anne
中科院分区：
文献类型：
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作者：
Daugherty, Aaron C.;Yeo, Robin W.;Brunet, Anne
染色质可及性是基因组调控的一个重要组成部分，主要是在同质和简单的系统中进行研究，例如分离的细胞群体或早期发育模型。染色质可及性是否可以在体内复杂的动态系统中以高灵敏度进行评估，这在很大程度上仍未得到探索。在这项研究中，我们使用ATAC-seq来鉴定整个动物，即模式生物秀丽隐杆线虫从胚胎发育到成年期的染色质可及性变化。发育阶段之间染色质可及性的变化是高度可重复的，概括了组蛋白修饰的变化，并揭示了整个生物体发育过程中表观基因组景观的关键调控方面。我们发现超过5000个远端非编码区在发育阶段之间表现出染色质可及性的动态变化，因此可能代表假定的增强子。当在体内测试时，这些假定的增强子中的一些确实驱动了新的细胞类型和时间特异性表达模式。最后，通过在机器学习框架中整合转录因子结合基序，我们确定了EOR-1是一种独特的转录因子，可能在发育过程中调节染色质动力学。我们的研究为秀丽隐杆线虫提供了一个独特的资源，在这个系统中，增强子的普遍性和重要性仍然没有得到很好的表征，并证明了利用整个生物体染色质可及性来识别复杂系统中新的调控区域的能力。
Chromatin accessibility, a crucial component of genome regulation, has primarily been studied in homogeneous and simple systems, such as isolated cell populations or early-development models. Whether chromatin accessibility can be assessed in complex, dynamic systems in vivo with high sensitivity remains largely unexplored. In this study, we use ATAC-seq to identify chromatin accessibility changes in a whole animal, the model organism Caenorhabditis elegans, from embryogenesis to adulthood. Chromatin accessibility changes between developmental stages are highly reproducible, recapitulate histone modification changes, and reveal key regulatory aspects of the epigenomic landscape throughout organismal development. We find that over 5000 distal noncoding regions exhibit dynamic changes in chromatin accessibility between developmental stages and could thereby represent putative enhancers. When tested in vivo, several of these putative enhancers indeed drive novel cell-type-and temporal-specific patterns of expression. Finally, by integrating transcription factor binding motifs in a machine learning framework, we identify EOR-1 as a unique transcription factor that may regulate chromatin dynamics during development. Our study provides a unique resource for C. elegans, a system in which the prevalence and importance of enhancers remains poorly characterized, and demonstrates the power of using whole organism chromatin accessibility to identify novel regulatory regions in complex systems.