Chromatin accessibility dynamics across C. elegans development and ageing [ChIP-seq]

An essential step for understanding the transcriptional circuits that control development and physiology is the global identification and characterization of regulatory elements. Here we present the first map of regulatory elements across the development and ageing of an animal, identifying 42,245 elements accessible in at least one C. elegans stage. Based on nuclear transcription profiles, we define 15,918 protein-coding promoters and 17,918 putative enhancers, and find that both types of element can drive orientation-independent transcription. Additionally, hundreds of promoters produce transcripts antisense to protein coding genes, suggesting involvement in a widespread regulatory mechanism. We find that the accessibility of most elements is regulated during development and/or ageing and that patterns of accessibility change are linked to specific developmental or physiological processes. The map and characterization of regulatory elements across C. elegans life provides a platform for understanding how transcription controls development and ageing. ChIP-seq was used to profile H3K4me3, H3K4me1, H3K36me3, and H3K27me3 across development

解析调控发育与生理过程的转录调控环路，全局鉴定并表征调控元件是其中的核心环节。本研究首次构建了动物全生命周期发育与衰老过程中的调控元件图谱，共鉴定出42245个至少在秀丽隐杆线虫（C. elegans）某一发育阶段可及的染色质调控元件。基于细胞核转录组谱，我们共定义了15918个蛋白编码启动子与17918个潜在增强子，并发现这两类元件均可驱动方向非依赖性转录。此外，数百个启动子可产生与蛋白编码基因反向互补的转录本，提示其参与了一类广泛存在的调控机制。我们还发现，绝大多数调控元件的染色质可及性在发育和/或衰老过程中受到精准调控，且可及性变化模式与特定的发育或生理过程密切相关。秀丽隐杆线虫全生命周期调控元件的图谱构建与特征注释，为解析转录调控如何控制发育与衰老过程提供了重要研究平台。本研究采用染色质免疫共沉淀测序（ChIP-seq）技术，对发育全过程中的H3K4me3、H3K4me1、H3K36me3及H3K27me3组蛋白修饰进行了谱型分析。